Hepatology Clinical Studies

U-M Hepatology Program Join a Clinical Study

Clinical studies help to find better treatments and diagnostic tests that may benefit future patients. Some studies may provide participants early access to newer treatments.

  • the ability to be given a new intervention that may be better or have fewer side effects than their current treatment
  • gaining a better understanding of their disease or condition
  • additional advice, care, and support from trained clinical staff who understand the disease or condition

Partner with us as we advance medicine. Search our clinical studies below!

  • If you have any questions about one of our clinical studies, please contact the study coordinator, whose name appears at the end of the description of each study.

Cirrhosis

Non-Pharmaceutical Intervention for Cirrhotic Cramps Reduction: The NICCles Trial

Enrollment status: OPEN

Primary Objective

To determine the feasibility and efficacy of using a non-pharmaceutical treatment to improve the symptoms and severity of muscle cramps in patients with cirrhosis. Muscle cramps are common and distressing to patients. Consistent with prior studies, we found that >2/3 of patients of a group of 305 patients with cirrhosis surveyed experienced severe muscle cramps within the prior month. Cramps lead to a cascade of deleterious consequences. Cramps cause pain, interfere with sleep, and limit mobility. Although the treatment of cramps has been explored in multiple studies, safe, effective treatments for cramps remain limited. Approaches studied in clinical trials include vitamin E (frequently ineffective), quinine (effective but has a black box warning for blood disorders), baclofen (possibly effective but sedating), albumin infusion (possibly effective but expensive), and taurine (possibly effective but expensive and unregulated). Better interventions and studies are needed.

Inclusion criteria

  • Adult ≥18 years of age
  • Diagnosis of cirrhosis based on one or more of the following:
    • Histology
    • Radiographic or elastographic evidence of cirrhosis
    • Esophageal or gastric varices on endoscopy AND presence of chronic liver disease
  • History of cramps via affirmative answers to these 3 questions:
    • Do you have painful muscle spasms, cramps, or charley horses that come on while resting?
    • Did muscle cramps happen at least four times in the past month?
    • Do the muscle cramps bother you?

Exclusion criteria

  • Non-English speaking
  • Unable or unwilling to provide consent
  • History of liver transplant
  • History of multiple sclerosis
  • History of cerebral palsy
  • History of stroke with paralysis

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


CAREGIVER: A randomized controlled trial to improve the burden and distress of caring for persons with decompensated cirrhosis

Enrollment status: OPEN

Primary objective

Caregivers of patients with cirrhosis suffer from a high burden, which may influence their quality of life. Cirrhosis patients often rely on caregivers to assist them with daily activities including transportation, managing medical care, bathing and dressing, managing finances and taking care of other household activities. The diverse responsibilities of caregiving create physical and psychological strain. This can affect the health of the caregiver and the patient. For caregivers of cirrhosis patients, this can lead to a decrease in quality of life, unemployment and even an inability to care for one’s own medical problems. The well-being of cirrhosis caregivers is an unmet need. Unfortunately, treatments directed towards caregivers of persons with advanced cirrhosis are limited. 

This research study is comparing the effectiveness of two treatments as a way of improving the quality of life of taking care of persons with cirrhosis. The two different behavioral interventions we are testing are called written emotional disclosure and resilience training. It has been well documented that putting personal experiences into a story, whether in written or spoken form, is associated with both physical and mental benefits across diverse populations. Similarly, the caregiver’s burden itself may benefit from a re-framing through the tools of positive psychology and resilience training.

Inclusion criteria

  • Adult ≥18 years of age
  • Primary informal caregiver for a patient with a clinical diagnosis of decompensated cirrhosis

Exclusion criteria

  • Non-English speaking
  • Unable or unwilling to provide consent
  • Severe cognitive impairment
  • Caregiver is participating in another interventional study
  • Caregiver has used a personal diary within the past 12 months

Study design

In order to determine whether written emotional disclosure and resilience training reduces burden and distress among primary caregivers of patients with decompensated cirrhosis, we are testing two separate interventions in a three-arm parallel group, randomized-controlled efficacy trial of 90 primary informal caregivers.

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


Medically tailored meals to prevent recurrent hepatic encephalopathy: The BRAINFOOD pilot trial

Enrollment status: OPEN

Primary objective

Hepatic encephalopathy is caused by brain exposure to ammonia, a waste product of bacterial metabolism in the gut. Normally the liver converts ammonia to urea. In cirrhosis, however, ammonia is distributed peripherally. Muscle is the main auxiliary site of ammonia clearance. Ammonia detoxification by muscle consumes branched-chain amino acids that are liberated in a catabolic process. A vicious cycle emerges. Hyperammonemia begets sarcopenia which, in turn, raises blood ammonia levels. Sarcopenia is present in ≥50% of patients with cirrhosis. Contrary to the widely held myth that excess protein intake raises ammonia levels and HE risk, increased protein intake is safe in patients with cirrhosis including those with history of HE. To reduce recurrent hepatic encephalopathy, patients are recommended to consume a high protein diet. Nutrition is a central component in management of cirrhosis complications. Guidelines recommend that patients with HE receive ahigh protein diet. Protein supplementation has been shown to improve health related quality of life and to reduce the risk of HE. One solution to the problem of malnutrition and therefore recurrent HE is to provide standardized meals for the short-term during the high-risk period after an HE episode. The BRAINFOOD study seeks to determine whether home-delivered high protein MTM is feasible and if it can reduce recurrent hepatic encephalopathy in patients with a recent episode of overt hepatic encephalopathy.

Inclusion criteria

  • Adult ≥18 years of age
  • Diagnosis of cirrhosis based on one or more of the following:
    • Histology
    • Radiographic or elastographic evidence of cirrhosis
    • Esophageal or gastric varices on endoscopy AND presence of chronic liver disease

Exclusion criteria

  • Non-English speaking
  • MELD Score >20
  • Pregnancy (self-reported)
  • Unable or unwilling to provide consent
  • History of liver transplant
  • Current or planned admission to a nursing facility
  • Serum creatinine >2.0 mg/dL (with the exception that we will include patients with a serum creatinine >2.0 mg/dL if they are receiving hemodialysis)
  • Disorientation at the time of enrollment
  • Barcelona-Clinic Liver Cancer (BCLC) Stage D Hepatocellular Carcinoma with Child-Turcotte Pugh (CTP) Class C
  • History of eating disorder

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


National Cancer Institute Early Detection Research Network (EDRN) Hepatocellular Carcinoma Early Detection Study (HEDS)

Enrollment status: CLOSED, follow-up ongoing

Primary objective

To determine the incidence rate and the performance of ultrasound, and the biomarkers, alpha-fetoprotein (AFP), AFP-L3%, and des-gamma carboxy-prothrombin (DCP), in detecting preclinical hepatocellular carcinoma (HCC), as well as evaluate the performance of novel biomarkers for the detection of preclinical HCC.

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥18 years of age
  • Diagnosis of cirrhosis based on:
    • Histology
    • US, MRI or CT showing cirrhotic appearing liver with splenomegaly and platelet count of <120 mm3
    • Elastography, done by ultrasound or MRI showing a cirrhotic liver
    • A FibroTest result of F4 (stage 4), indicating cirrhosis
    • Varices on endoscopy or an abdominal imaging test AND presence of chronic liver disease

Main exclusion criteria

  • Ongoing significant hepatic decompensation
  • Listed for liver transplant as “exception”
  • AIDS related diseases
  • Cancer history in last 5 years (excluding non-melanoma skin cancer)
  • Immunosuppressive therapy

Principal investigator: Neehar Parikh, MD, MS • ndparikh@med.umich.edu

Study coordinator: Austin Fobar, MS, MPH • afobar@med.umich.edu


PAL-LIVER study (PALiative Care for LIVER disease): Introducing palliative care (PC) within the treatment of end stage liver disease (ESLD): A cluster randomized controlled trial

Enrollment status: OPEN

Primary objective

To assess the comparative effectiveness of two Palliative Care Delivery models for patients with end stage liver disease on improving quality of life (QOL).

Main inclusion and exclusion criteria

Patients willing to participate will be asked to select a caregiver to participate in the study. A caregiver is defined as someone who knows the patient well and is involved in their routine medical care. A caregiver must consent and be willing to attend the initial intervention visit along with the patient.

Inclusion criteria: Patients

  1. Age >18 years old
  2. Patient and Caregiver willing to sign informed consent
  3. Able to read/understand English
  4. Either of the following two clinical criteria:
    1. CTP Class B or C cirrhosis with one of the following (new or ongoing) within the prior 6 months from the date of consent:
      1. Ascites (requiring diuretics)
      2. Spontaneous bacterial peritonitis (SBP)
      3. Hepatic hydrothorax (requiring diuretics)
      4. Variceal bleed (with 1 or more recurrences)
      5. Overt hepatic encephalopathy (requiring medications)
      6. Type 2 hepatorenal syndrome
    2. Hepatocellular Cancer (HCC)
      1. Any BCLC (except Stage D) with CTP class B OR
      2. BCLC Stage C with CTP class A

Exclusion criteria: Patients

  1. Hepatologist-estimated life expectancy of less than 6 months
  2. Prior liver transplant
  3. MELD>30 at the time of enrollment
  4. Patients who, in the judgment of the investigator, are likely to undergo liver transplantation within 3 months of enrollment
  5. Lacks capacity to provide informed consent, including those with stage 2 HE or higher at the time of consent
  6. Patients who are already receiving, or who have received palliative care prior to study entry (within the past 1 year)

Inclusion criteria: Caregivers

  1. Identified caregiver of ESLD patients
  2. Age >18 years old
  3. Able to read/understand English
  4. Providing direct care for at least >10 hours per week

Exclusion criteria: Caregivers

  1. Impaired cognitive function

Study design

This is a two-armed cluster randomized controlled trial (RCT). Randomization will take place at the level of clinical centers, and will be stratified by VA vs non-VA. Each arm will have 7 clinical centers. Standardized protocols (including visit agenda) will be followed at each of the clinical centers to maintain intervention fidelity across sites.

Model 1: Consultative PC (i.e., consultation with a board-certified or board-eligible PC specialist provider)

Model 2: Trained hepatologist-led PC intervention (i.e., hepatologist trained to deliver PC services)

The University of Michigan is a hepatologist-led site (Model 2).

All patients and caregivers participating in this study will receive palliative care intervention at an initial visit, followed by 1, 2, and 3 months. The intervention will comprise an approach to render palliative care, as taught to hepatologists through an on-line learning platform.  The elements of the intervention will follow a palliative care checklist, to include:

  1. Patient/caregiver understanding of diagnosis, illness, and prognosis
  2. Symptom assessment and management
  3. Psychosocial assessment and management
  4. Distress screening and management
  5. Discussion of goals of care
  6. Advanced directives

The intervention is delivered over the course of initial, 1, 2, and 3 month visits, each approximately one hour in duration.

Principal investigator: Elliot Tapper, MD • etapper@med.umich.edu

Contact person: Samantha Nikirk • (734) 232-4182 • samjwalk@med.umich.edu


Safety and efficacy of terlipressin in hepatorenal syndrome (HRS) type 1

Enrollment status: OPEN

Objective

This is a phase 3, randomized, double-blind, placebo-controlled, multicenter trial to confirm the safety and efficacy of terlipressin in subjects with hepatorenal syndrome (HRS) type 1. HRS type 1 is a rare condition that can occur in patients with cirrhosis, decompensated liver disease, and portal hypertension. HRS type 1 is characterized by rapid progressive renal injury and has a very poor prognosis with >80% mortality within 3 months. At present, there are no approved drug therapies for HRS type 1 in the United States or Canada. The only cure for HRS type 1 and the underlying end-stage cirrhosis is liver transplantation; however, many patients will not survive long enough to receive a liver transplant. Terlipressin is an investigational vasoconstrictive drug that may improve renal function in patients with HRS type 1. There is substantial data available from many published clinical investigations that provide compelling evidence of terlipressin's efficacy in patients with HRS type 1.

Michigan Medicine is one of sites that is actively enrolling subjects for this clinical trial. A total of 300 subjects are planned to be enrolled at about 70 sites in the United States and Canada. For more information about this trial, please see https://clinicaltrials.gov/ct/show/NCT02770716.

Inclusion criteria

  • Adult patients (outpatients and inpatients) >18 years of age at Michigan Medicine
  • Patients with chronic liver disease – cirrhosis + ascites
  • Patients with acute renal failure (worsening serum creatinine within last two weeks reaching 2.25 mg/dL or above)
  • No granular casts on urine microscopy, proteinuria < 500 mg/day
  • Able and willing to provide an informed consent

Exclusion criteria

  • Patients with renal failure caused by acute tubular necrosis (ATN), nephrotoxic drugs, or contrast-induced injury
  • Renal replacement therapy
  • Unable and unwilling to provide an informed consent

For full inclusion and exclusion criteria, please inquire.

Contact person:


Preferences of patients undergoing surveillance of hepatocellular carcinoma

Enrollment status: OPEN

Objective

Analyze patient perspective on various aspects of surveillance for and therapy of HCC through the use of conjoint methodology

Main inclusion criteria

  • Able and willing to provide written informed consent
  • Age ≥ 18 years of age
  • Undergoing HCC surveillance due to cirrhosis or HBV diagnosis

Exclusion criteria

  • History of or current diagnosis of HCC
  • Active hepatic encephalopathy
  • No English
  • Dementia or other type of cognitive impairment

Principal investigator: Neehar Parikh, MD, MS • ndparikh@med.umich.edu

Study coordinator: Austin Fobar, MS, MPH • afobar@med.umich.edu

Drug-Induced Liver Injury

Idiosyncratic liver injury associated with drugs (ILIAD): A retrospective study

Enrollment status: OPEN

The goal of the ILIAD protocol is to create a database and bank of biological specimens (DNA, plasma, lymphocytes) from individuals with severe drug-induced liver injury (DILI) due to drugs, or herbal and dietary supplements (HDS) and complementary and alternative medications (CAM) after January 1, 1994. This study is funded by the NIH/NIDDK.

Study design

  • Telephone or personal interview of medical history surrounding DILI event
  • Single blood draw
  • Participant receives up to $100

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu


A multi-center, longitudinal study of drug-induced and complementary and alternative medication—induced liver injury

Enrollment status: OPEN

The goal of this multicenter NIH study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications (CAM) within 6 months of onset. Clinical data, blood, DNA, and urine will be collected from affected patients and matched controls for mechanistic and genetic studies.

Study design

  • All subjects have a baseline and 6-month follow-up visit at Michigan Medicine, which includes surveys, medical history, and blood and urine collection.
  • Patients with liver injury at 6 months return for 12-, 36-, and 48-month visits.

Costs

  • Costs of study lab tests provided by sponsor (NIDDK).
  • Subjects receive $50 for each completed study visit.

Contacts for referrals or questions:

Principal investigator: Robert Fontana, MD • rfontana@med.umich.edu


For more information on drug-induced liver injury, see the following websites:

Drug-Induced Liver Injury Network: http://www.dilin.org

NIDDK LiverTox website: http://www.livertox.nih.gov/

Hepatitis B

NIH Hepatitis B Research Network

In September 2008, the NIH launched a Hepatitis B Research Network (http://www.hepbnet.org) comprised of 29 clinical centers (adult and pediatric), a data coordinating center, and an immunology laboratory. The University of Michigan is one of the clinical centers and Dr. Anna Lok chairs the network's steering committee.

This network conducts observational studies as well as clinical studies of new treatment strategies.

Hepatitis B Research Network — Observational Study

Enrollment status: CLOSED

Objective

To study the pattern of hepatitis B in North America and the rates of transition through different phases of chronic HBV infection

Inclusion criteria

  • Adult patients with hepatitis B who are currently not on any antiviral therapy for hepatitis B (exception: pregnant women).

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu


Hepatitis B Research Network — Immune-Active Trial

Combination therapy of peginterferon alfa-2a and tenofovir versus tenofovir monotherapy in HBeAg-positive and HBeAg-negative chronic hepatitis B

Enrollment status: CLOSED

Objective

To compare the long-term efficacy of initial treatment with combination therapy consisting of peginterferon alfa-2a plus tenofovir DF versus tenofovir DF monotherapy.

Inclusion/exclusion criteria

  • Adults with chronic hepatitis B infection, slightly abnormal liver enzyme levels (ALT >45 IU/mL for males and >30 IU/mL for females), no or limited previous antiviral treatment.
  • Patients with cirrhosis can be included provided no liver failure
  • Normal kidney function, no major medical or psychosocial illnesses, can tolerate interferon

Study design

This is a randomized (1:1) trial comparing

  1. Tenofovir DF 300 mg daily for 192 weeks (4 years) and
  2. Peginterferon alfa-2a 180 µg weekly for 24 weeks plus tenofovir DF 300 mg daily for 192 weeks (4 years).

Note: The cost of medications, clinical evaluations, and tests associated with the study will be covered.

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu 


TARGET HBV: An observational study of patients undergoing therapy for chronic hepatitis B (HBV) infection

Enrollment status: CLOSED

Objective

The purpose of this research is to learn more about people who have been diagnosed with hepatitis B and how they are managed in clinical practice.

Inclusion criteria

  • Adult patients with hepatitis B who are on a stable antiviral therapy regimen for hepatitis B

Study design

  • Data extracted from medical records
  • Participants complete survey
  • No research-specific visits

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu

Hepatitis C

Hepatitis C therapeutic registry and research network (HCV-TARGET) – a longitudinal, observational study

Sponsor: University of Florida, University of North Carolina

Enrollment status: HCV+ Donor Recipient Sub-Study - Open

Eligibility criteria

  • Any HCV patient receiving direct-acting antiviral drug therapy
  • Transplanted with HCV nucleic acid test (NAT) positive donor solid organ (all solid organs including but not limited to liver, kidney, heart, lung, and pancreas)
  • HCV antibody negative at the time of organ transplantation

Objective

To collect and study information on patients with chronic hepatitis C virus who are being treated with direct-acting antiviral agents in a “real world” patient population to determine:

  • Effectiveness of these drugs in differing patient populations
  • Compare treatment durations in differing groups of patients
  • How best to manage side effects
  • Genetic variances in drug response
  • Drug-to-drug interactions
  • Patient education — group versus individual
  • Pharmacy usage
  • Drug resistance

Principal investigator: Anna Lok, MD • aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu 

Hepatocellular Carcinoma

A 5-year longitudinal observational study of patients with hepatocellular carcinoma (TARGET–HCC)

Sponsor: TARGET PharmaSolutions

Enrollment status: OPEN

Objective

The goal of this research study is to observe the clinical course of patients diagnosed with HCC in a "real-life" setting. Researchers are interested in collecting information and blood/tissue samples in order to develop predictors of disease progression.

Inclusion criteria

  • Adult patients (age > 18 years) with any history of HCC diagnosed by imaging or pathology within the last 3 years

Exclusion criteria

  • None

Study design

  • Medical records will be collected from date of consent going back 3 years and forward 5 years from the date of consent.
  • Optional Patient-Reported Outcome Survey annually
  • Optional Biorepository Specimen Bank annually. Patients who agree to participate in the Biorepository Specimen Bank will be paid $25 for each blood draw.
  • Optional Post-Authorization Safety Study of Early Recurrence of Hepatocellular Carcinoma in HCV-Infected Patients after Direct-Acting Antiviral Therapy
    • This study will also look at data from a specific period of time for patients with hepatitis C following successful HCC treatment and compare information from those who get direct-acting antiviral drugs to treat their hepatitis C to those who do not get direct-acting antiviral drugs. People who have a specific type or degree of HCC and meet the sub-study requirements, including having hepatitis C, may be asked to participate.

Principal investigator

Contact person


Blood Sample Collection to Evaluate Biomarkers for Hepatocellular Carcinoma

Sponsor: Exact Sciences

Enrollment Status: CLOSED

Objective

The primary objective of this study is to obtain de-identified, clinically characterized whole blood specimens for use in developing and evaluating the performance of new biomarker assays for detection of hepatocellular carcinoma (HCC).

Inclusion Criteria

  • HCC Subjects
    • Subject has a recent (within 6 months of enrollment) untreated clinically diagnosed hepatocellular carcinoma as defined by ≥1 cm lesion exhibiting arterial phase hyperenhancement in combination with washout appearance and/or capsule by 4 phase CT scan or multiphase contrast enhanced MRI or biopsy is positive for HCC.
  • Control
    • Non-cancer subject undergoing routine imaging surveillance for HCC
    • Definitive lack of HCC within 3 months prior to enrollment as defined by negative imaging, for HCC.
      • Control Group 1 - negative by ultrasound
      • Control Group 2 - negative by CT or MRI

Exclusion Criteria

  • Known cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers).
  • Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
  • Prior or current treatment with sorafenib, regorafenib, or other treatment indicated for HCC.
  • Any HCC treatment prior to enrollment/blood sample collection (e.g., surgery, ablation, embolization, pharmacotherapy, radiotherapy, liver transplant or other treatment indicated for HCC).
  • IV contrast (e.g. CT and MRI) within 1 day [or 24 hours] of blood collection.
  • Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
  • Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
  • Individual has a condition the Investigator believes would interfere with his or her ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.

Study Design

Subjects with untreated hepatocellular carcinoma (HCC) and subjects undergoing HCC surveillance will be enrolled and have blood samples collected. Subjects undergoing HCC surveillance will be followed for up to 6 months. Another blood sample will be collected at the 6-month visit which will be scheduled no longer than 6 months from enrollment.

Principal Investigator

Contact Person


Michigan Hepatocellular Carcinoma Early Detection Study

Enrollment status: OPEN

Objective

The aim of this study is to create an ongoing biorepository of longitudinally collected biospecimens from a cohort of cirrhosis patients, that will form a reference set to be used for future biomarker validation research.

Inclusion Criteria

  • Age ≥ 18 years of age
  • Ultrasound or other imaging within 6 months prior to consent showing no liver mass
  • Diagnosis of cirrhosis based on history of hepatic decompensation, histology, imaging, or elastography

Exclusion Criteria

  • Clinical evidence of significant hepatic decompensation:
    • Refractory ascites requiring paracentesis
    • Overt encephalopathy requiring lactulose or rifaximin
    • Hepatorenal syndrome
    • Child Class C
  • History of HCC
  • Significant co-morbid medical conditions with life expectancy less than one year
  • Cancer history within the last 2 years (excluding non-melanoma skin cancer)
  • Prior solid organ transplant

Study Design

  • Blood samples will be collected on the day of consent, at 6 months, and yearly thereafter.
  • If a liver biopsy is indicated for clinical care, any surplus tissue specimen will be collected.
  • Alcohol and tobacco questionnaire will be administered at baseline, and an Audit-C questionnaire will be administered at follow-up visits.

Principal investigator

Study coordinator


Biorepository of Blood and Liver Tumor Tissue Samples

Enrollment status: OPEN

Objective

The aim of this study is to create an ongoing biorepository of blood samples and liver tumor tissue to help identify protein and genetic signatures that may improve diagnostic and prognostic capabilities in patients with liver cancers.

Inclusion Criteria

  • Patients with hepatocellular carcinoma or colorectal metastases to the liver (patients with CRC metastases eligible if they received prior systemic chemotherapy or resection of primary tumor); ages 18-99

Exclusion Criteria

  • None

Study Design

  • Blood samples will on the day of consent, at 6 months and yearly thereafter.
  • We will measure QOL using the PROMIS Global Health Scale and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) instrument (Appendix 3.) The Global Health Scale is derived from the PROMIS assessment center and provides a 10-item assessment of global health related QOL within the 7 days of assessment.

Principal Investigator

Contact Person

Liver Transplant

Improving Kidney Outcomes in Liver Transplant Recipients

HUM00115731 & HUM00119820

Enrollment status: OPEN

Objective

Liver transplantation (LT) is the standard of care for decompensated cirrhosis. These patients are at a higher risk of developing chronic kidney disease after LT associated with high morbidity, mortality and healthcare costs. Patient-level interventions directed at risk factors have shown to improve health outcomes in chronic diseases. The feasibility of these interventions in improving patient outcomes has not been studied among LT recipients. Our overarching goal is to improve kidney outcomes among liver transplant recipients. The aims of this study are to assess the knowledge of chronic kidney disease knowledge among liver transplant recipients and examine the effect of personalized intervention(s) targeting the risk factors for chronic kidney disease on kidney function.

Inclusion criteria

  • Adult patients >18 years of age (out-patients and in-patients) at the University of Michigan
  • Patients who have received liver transplants between 2005 and 2016
  • Patients who are at least 3 months after transplant
  • Able and willing to provide an informed consent

Exclusion criteria

  • Unable and unwilling to provide an informed consent

For full inclusion and exclusion criteria, please inquire.

Contact Persons

Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH)

A Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-finding study to evaluate the efficacy and safety of CC-90001 in subjects with non-alcoholic steatohepatitis (NASH) and stage 3 or stage 4 liver fibrosis

Sponsor: Celgene Corporation

Enrollment status: OPEN 

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04048876

Brief summary

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, dose-finding study evaluating the efficacy of three treatment doses of CC-90001 (100 mg, 200 mg and 400 mg oral daily), compared with placebo, in non-alcoholic steatohepatitis (NASH) subjects with Stage 3 and Stage 4 fibrosis. This study is designed to assess response to treatment on measures of fibrosis and other efficacy parameters. It will also assess dose response and overall safety.

Inclusion criteria

  • Diagnosis of NASH with presence of Stage 3 or 4 fibrosis

Exclusion criteria

  • History or evidence of decompensated liver diseaseHepatitis and fibrosis more likely related to etiologies other than NASH
  • Subject has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening
  • History or positive screen for HIV infection or congenital or HIV-unrelated acquired immunodeficiencies
  • History of hepatitis B and/or hepatitis C
  • History of malignancy
  • Pregnancy or lactation

Principal Investigator: Hari Conjeevaram, MD

Contact person: CTSU-ACD-Coordinators@med.umich.edu


A 5-year longitudinal observational study of patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (TARGET-NASH)

Sponsor: TARGET PharmaSolutions

Enrollment status: OPEN

Objective

The goal of this research study is to observe any treatment for NAFLD/NASH in a large number of people in a "real-life" setting. Researchers are interested in observing how lifestyle changes, counseling, or other treatments work in patients who are treated by their doctors in routine practice.

Inclusion criteria

  • NAFLD diagnosed by imaging
  • NASH diagnosed by liver biopsy OR by imaging + elevated ALT + 1 or more of the following: obesity, type 2 diabetes, dyslipidemia

Exclusion criteria

  • Other chronic liver disease, including alcohol-induced liver disease
  • Current participation in another NASH registry or clinical trial

Study design

  • Patients will be followed for up to 5 years. Medical records will be collected
  • Optional Patient Reported Outcome Survey annually
  • Optional Biorepository Specimen Bank annually. Patients who agree to participate in the Biorepository Specimen Bank will be paid $25 for each blood draw.

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu


University of Michigan–Peking University Joint Initiative

Role of visceral adiposity in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in lean versus obese patients: A comparative study between patients at University of Michigan Health System versus Peking University Health Science Center

Enrollment status: CLOSED

Objective

To use a novel technique, analytic morphomics, to quantify visceral adipose tissue, ectopic adipose tissue and quality of fat in lean persons with NAFLD versus lean persons with no NAFLD and obese persons with NAFLD to understand why some lean persons develop fatty liver and to understand the role of fat in the abdomen on development of fatty liver.

Inclusion criteria

  • Adults 18+ with nonalcoholic fatty liver disease

Exclusion criteria

  • Other causes of liver disease (hepatitis B, hepatitis C, alcohol, etc)
  • Other causes of fat in the liver
  • History or plans to undergo bariatric surgery
  • Current use of weight reduction medications
  • Liver failure or liver cancer
  • Women who are pregnant

Study design

  • Subjects will undergo a thin slice CT scan to capture images of the abdomen and to apply analytic morphomics (special computer analysis) to measure quantity and quality of fat in abdomen
  • Subjects will give blood samples to test for markers of fatty liver, glucose and lipid levels
  • Subjects will complete 3 diet recalls
  • Compensation provided

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Sravanthi Kaza, (734) 615-3853 or sravanth@med.umich.edu


A randomized controlled pilot trial of a structured mobile technology based lifestyle program vs usual care for patients with nonalcoholic fatty liver disease

Enrollment status: OPEN

Objective

The aim of this study is to compare the effectiveness of usual care to a mobile technology based lifestyle intervention on change in liver and metabolic related parameters. Additionally, the study aims to identify predictors associated with reduction in hepatic steatosis and weight loss.

This is a structured mobile technology (Fitbit)-based study of NAFLD patients evaluated and managed in the Michigan Medicine Hepatology Clinic. Clinical data collection and surveys will be administered during a routine clinic visit or during an elective research visit through the clinical research center at baseline, at 6 months and 12 months follow-up visits. Patients in the intervention arm will receive the Fitbit during their baseline clinic visit and patients in the usual care arm will receive the Fitbit during their 6-month follow-up visit. The Fitbit will be used to track physical activity of patients in both arms for a total of 6 months each. During their Fitbit trial, patients will also be provided with personalized weekly feedback on step count.

Inclusion criteria

  • Adult patients over 18 years old
  • Diagnosis of NAFLD or nonalcoholic steatohepatitis (NASH)
  • Ability to communicate in English as primary language
  • Able to give informed consent
  • Must be able to participate in basic physical activity (i.e., regular walking)

Exclusion criteria

  • Significant alcohol use (defined based on clinical diagnosis or report of >7 drinks per week in women and >14 drinks per week in men)
  • Co-existing liver disease, such as viral hepatitis B or C, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, Wilson disease, or alcohol-related liver disease.
  • Evidence of hepatic decompensation (past or present), including variceal bleeding, ascites, hepatic encephalopathy, or hepatocellular carcinoma
  • Inability to make dietary modifications due to significant medical co-morbidity (including but not limited to severe, uncontrolled diabetes)

Principal investigator: Monica Tincopa, MD, MSc, tincopa@med.umich.edu

Contact person: Haila Asefa, (734) 232-0284 or asefa@med.umich.edu


Nonalcoholic Fatty Liver Disease Blood and Tissue Repository

Enrollment status: OPEN

Objective

The aim of the study is to develop a repository of blood (plasma and serum), liver tissue and clinical information from patients who are diagnosed with NAFLD or NASH. The samples will be stored indefinitely and utilized for future research to better understand clinical phenotypes of NAFLD/NASH, and better predict disease progression, as well as guide the management of future patients

Inclusion criteria

  • Adult patients over 18 years old
  • Ability to communicate in English as a primary language
  • Diagnosis of NAFLD or NASH

Exclusion criteria

  • Significant alcohol use (defined based on clinical diagnosis or report of >7 drinks per week in women and >14 drinks per week in men)
  • Co-existing liver disease, such as viral hepatitis B or C, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, Wilson disease, or alcohol-related liver disease.
  • Current or prior history of decompensated cirrhosis: variceal bleeding, ascites, hepatic encephalopathy, or hepatocellular carcinoma
  • Medications known to cause hepatic steatosis or other alternative causes of hepatic steatosis: mediations include steroids, tamoxifen, amiodarone, certain highly active anti-retroviral therapy (HAART), valproate, methotrexate.
  • Active substance abuse or psychiatric disease
  • Current participation in pharmacological clinical trial for NAFLD/NASH. Those with prior participation are eligible.
  • Pregnancy

Principal investigator: Monica Tincopa, MD, MSc, tincopa@med.umich.edu

Contact person: Haila Asefa, (734) 232-0284 or asefah@med.umich.edu

Primary Biliary Cholangitis (PBC)

A Phase 4, double-blind, randomized, placebo-controlled study evaluating the pharmacokinetics and safety of obeticholic acid in patients with primary biliary cholangitis and moderate to severe hepatic impairment

Sponsor: Intercept Pharmaceuticals

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03633227

Enrollment status: OPEN

Brief summary

This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics (PK) and safety of obeticholic acid (OCA) treatment in patients with primary biliary cholangitis (PBC) and moderate to severe hepatic impairment over a 48-week treatment period. Patients who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized patients have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all patients receive OCA will be considered following review of blinded safety and PK data 

Inclusion

  • A definite or probable diagnosis of PBC
  • Evidence of cirrhosis
  • Satisfy the criteria of the method of Child–Pugh classification for hepatic impairment during Screening
  • MELD score of 6 to 24 at Screening
  • Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for ≥3 months)

Exclusion

  • Non-cirrhotic or cirrhotic Child–Pugh A
  • History of liver transplant or organ transplant
  • History of alcohol or drug abuse within 12 months prior to screening
  • Hepatic encephalopathy

Principal investigator: Frederick Askari, MD, PhD faskari@med.umich.edu

Contact person: CTSU-ACD-Coordinators@med.umich.edu


TARGET PBC

A 5-year longitudinal observational study of patients with primary biliary cholangitis

Enrollment status: CLOSED

Objective

The purpose of this research is to learn more about people who have been diagnosed with primary biliary cholangitis and how they are managed in clinical practice.

Inclusion criteria

  • Adult patients who are being treated or managed for primary biliary cholangitis

Study design

  • Data extracted from medical records
  • Participants complete optional surveys and annual blood sample
  • No research-specific visits

Principal investigator: Anna Lok, MD aslok@med.umich.edu

Contact person: Sravanthi Kaza: (734) 615-3853 • sravanth@med.umich.edu

Primary Sclerosing Cholangitis (PSC)

A randomized, double-blind, dose-ranging, placebo-controlled, Phase 2a evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with primary sclerosing cholangitis (PSC) and suspected liver fibrosis (INTEGRIS-PSC)

Sponsor: Pliant Therapeutics

Enrollment status: OPEN

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04480840

Brief Summary

A Phase 2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled, study to evaluate the safety, tolerability, and PK of PLN-74809 in participants with primary sclerosing cholangitis and suspected liver fibrosis

Eligibility

  • Established clinical diagnosis of large duct PSC based on an abnormal cholangiography
  • Suspected liver fibrosis assessed by ultrasound-based transient elastography
  • Serum ALP concentration > 1.5 times the upper limit of normal
  • Participants receiving treatment for IBD are allowed, if on a stable dose for at least 3 months
  • Serum AST and ALT concentration ≤ 5 times the upper limit of normal
  • If receiving treatment with UDCA, therapy is at a dose of < 25 mg/kg/day, has been stable for at least 3 months before screening

Principal investigator: Nataliya Razumilava, MD razumila@med.umich.edu

Study coordinator: CTSU-ACD-Coordinators@med.umich.edu


A Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of cilofexor in non-cirrhotic subjects with primary sclerosing cholangitis

ClinicalTrials.gov Identifier: NCT03890120

Sponsor: Gilead Sciences, Inc

Enrollment status: OPEN

Primary objective

To evaluate whether cilofexor (CILO, previously known as GS-9674) reduces the risk of fibrosis progression among non-cirrhotic subjects with primary sclerosing cholangitis (PSC).

Study design

The study will consist of a 10-week screening period, 96 weeks of treatment, and a follow-up visit 4 weeks after completion of treatment. Subjects will be randomized 2:1 to receive CILO 100 mg orally once daily or placebo for 96 weeks.

Key inclusion criteria

  1. Diagnosis of large duct PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC])
  2. Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0&endash;F3 fibrosis (according to the Ludwig classification) in the opinion of the central reader.
  3. For subjects on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable in the opinion of the investigator for at least 6months before screening. For subjects not on UDCA, no UDCA use for at least 6 months prior to screening.

Key exclusion criteria

  • Current or prior history of any of the following:
    • Cirrhosis as defined by any of the following:
      1. Liver biopsy demonstrating stage F4 fibrosis according to the Ludwig classification (or equivalent)
      2. Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage
      3. Liver stiffness > 20.0kPa by FibroScan®
    • Liver transplantation
    • Cholangiocarcinoma or hepatocellular carcinoma (HCC). If a dominant stricture has been identified, cholangiocarcinoma must be adequately excluded in the opinion of the investigator prior to Day 1.
    • Ascending cholangitis within 30 days of screening
  • Presence of a percutaneous drain or biliary stent
  • Child-Pugh (CP) score > 6 at screening, unless due to an alternative etiology such as Gilbert syndrome or therapeutic anticoagulation
  • Model for end-stage liver disease (MELD) score > 12 at screening, unless due to an alternate etiology such as therapeutic anticoagulation

Principal investigator: Pratima Sharma, MD, MS • pratimas@med.umich.edu

Study coordinator: Neha Shah, MBBS, CCRP • neshah@med.umich.edu

Blood, Tissue, and Urine Repositories

Liver Disease Blood and Tissue Repository

Enrollment status: OPEN

Objective

The main objective of the Liver Disease Blood and Tissue Repository is to facilitate clinical and translational research. The repository of blood samples (plasma and serum), liver tissue samples, and urine samples will be used by clinical and translational researchers to answer questions related to the pathophysiology and clinical outcomes of chronic liver disease. The samples will be used to evaluate the utility of available markers for the diagnosis and prognosis of various liver diseases, including fatty liver, viral hepatitis, and liver cancer, and to discover new biomarkers, such as biomarkers for liver fibrosis and liver cancer. We hope these studies will help us to better predict disease severity and progression of chronic liver disease and guide the management of patients in the future.

Inclusion criteria

  • All adult patients >18 years of age (out-patients and in-patients) undergoing a liver biopsy at the University of Michigan.
  • Patients with all liver diseases (acute or chronic) will be enrolled, including patients who are post-liver transplant.
  • Able and willing to provide an informed consent.

Exclusion criteria

  • Unable and unwilling to provide an informed consent.

Principal investigator: Anna Lok, MD, aslok@med.umich.edu

Contact person: Sravanthi Kaza, (734) 615-3853 or sravanth@med.umich.edu


Liver Transplant Blood and Urine Repository

HUM00100527

Enrollment status: OPEN

Objective

The rapid development of genomics, proteomics, and metabolomics have significantly increased the potential for productive translational research in transplantation, and many current research protocols in solid organ transplantation utilize blood and urinary specimens, in an effort to establish relationships between biologic markers, histological findings, and clinical outcomes. The main objective of the Liver Transplant Blood and Urine Repository is to facilitate clinical and translational research to utilize blood, cells and urine from patients who are candidates or have received a transplanted liver along with relevant medical record information to study clinical outcome and to discover new pathways and biomarkers to predict disease progression and guide future management.

Inclusion criteria

  • Living or deceased donor liver transplant candidates and recipients.
  • Male or female, 18 years or older.
  • Subject must be able to understand and provide informed consent.

Exclusion criteria

  • Recipients of multiple organ transplants, with the exception of simultaneous liver and kidney transplants.
  • Unable and unwilling to provide an informed consent.

For full inclusion and exclusion criteria, please contact the research staff.

Contact persons

Wilson Disease

A phase 3, randomized, rater-blinded, multicentre study to evaluate the efficacy and safety of ALXN1840 administered for 48 weeks versus standard of care in patients with Wilson disease aged 12 and older, with an extension phase of up to 60 months

Sponsor: Alexion Therapeutics

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT03403205

Enrollment status: CLOSED, follow-up ongoing

Brief summary

The purpose of this study is to evaluate the efficacy of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson disease patients aged 12 and older.

Principal investigator: Fred Askari, MD, PhD faskari@med.umich.edu

Study coordinator: CTSU-ACD-Coordinators@med.umich.edu


Clinical evaluation and assessment of instruments and biomarkers in subjects with Wilson disease

Sponsor: Ultragenyx Pharmaceutical

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04531189

Enrollment status: OPEN

Brief summary

The UX701-CL001 study aims to assess the utility and feasibility of various assessments and biomarkers to inform endpoint selection for future clinical studies, better understand the relationship between biomarkers and potential clinical outcomes, and characterize the clinical presentation of Wilson disease. UX701-CL001 is a clinical survey study. Subjects will complete assessments at the study site and at home to evaluate the clinical manifestations of Wilson disease in clinical and real-world environments.

Eligibility

  • Male or female ≥ 12 years of age
  • Confirmed diagnosis of Wilson disease
  • Documented history of copper chelator (ie, penicillamine, trientine) and/or zinc therapy or be ≥ 1 year post liver transplant with no active associated complications
  • Willing and able to comply with all study procedures and requirements

Principal investigator: Fred Askari, MD, PhD faskari@med.umich.edu

Study coordinator: CTSU-ACD-Coordinators@med.umich.edu


A Phase 2, single-arm, pathologist-blinded study using liver biopsy specimens to assess copper concentration and histopathologic changes in patients with Wilson disease who are treated with ALXN1840 for 48 weeks followed by an extension treatment period with ALXN1840 for up to an additional 48 weeks

Sponsor: Alexion Therapeutics

ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04422431

Enrollment status: OPEN

Brief Summary

The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). In the Treatment Period, efficacy and safety of ALXN1840 will be assessed at Week 48. Participants who complete the 48-week Treatment Period will be offered the opportunity to continue their treatment in a 48-week Extension Period that will offer additional time for evaluation of long-term efficacy and safety of ALXN1840. There will be no liver biopsies during the Extension Period.

Eligibility

  • Diagnosis of WD
  • Continuous treatment for WD with penicillamine, trientine, or zinc for at least 1 year prior to screening
  • Body mass index < 30
  • Able to cooperate with a percutaneous liver biopsy
  • Willing and able to follow protocol-specified contraception requirements

Principal investigator: Fred Askari, MD, PhD faskari@med.umich.edu

Study coordinator: CTSU-ACD-Coordinators@med.umich.edu