Michigan Genomics Initiative - MGI (HUM00071298)
PI: Chad Brummett, MD
Years of funding: 2012 - ongoing
Number of patients to be recruited: No target number
Study goals/aims: The Michigan Genomics Initiative (MGI) is a collaborative research effort among physicians and researchers at the University of Michigan with the goal of harmonizing patient electronic medical records with genetic data to gain novel biomedical insights. Current participation involves filling out a short questionnaire and giving a small blood sample. DNA is extracted from part of the aliquoted blood and genetically sequenced. The rest of the blood sample is stored securely at U-M. Patients consent to be contacted in the future for any applicable study conducted through U-M’s Central Biorepository.
Inclusion/Exclusion criteria: Currently, all patients 18 years of age or older undergoing surgery at the University of Michigan Health System are potentially eligible for participation in MGI.
Analgesic Outcomes Study II (AOS II) – A Longitudinal Study of Postsurgical Pain (HUM00106315)
PI: Chad Brummett, MD
Years of funding: 2010 – ongoing
Number of patients to be recruited: No target number.
Study goals/aims: AOS is a prospective, observational survey study of pain, mood, functional, and health outcomes.
Inclusion/Exclusion criteria: Currently, all patients 18 years of age or older undergoing ACL repair, ankle surgery, knee arthroscopy, shoulder surgery, total knee arthroplasty, total hip arthroplasty, distal arm and hand surgery, breast surgery, hysterectomy, inguinal hernia repair, myomectomy, prostatectomy, or thoracic surgery.
Mechanisms of the Centralized Pain Phenotypes - MiCAPP (HUM00120181)
PI: Daniel Clauw, MD; Chad Brummett, MD
Years of funding: 5 years
Number of patients to be recruited: 800 participants: There will be 200 participants in each treatment (OA, RA, CTS) condition, 100 FM patients, 100 healthy controls.
Study goals/aims: To better understand factors that influence health and pain. This can ultimately lead to better recommendations for more effective treatments based on an individual’s unique characteristics.
Aim 1 - To demonstrate that the current 2011 FM Survey Criteria predict non-responsiveness to peripherally-directed therapies, including:
a) surgery intended to relieve pain (hip arthroplasty, carpal tunnel release),
b) administration of a biologic agent to treat an autoimmune disorder (RA), and
c) acute and sub-acute administration of opioids (given to relieve pain immediately following hip arthroplasty and carpal tunnel release).
Aim 2 - To demonstrate that in all three cohorts, individuals with the highest FM Survey Criteria scores will have the most pronounced neurobiological findings associated with pain centralization, including abnormal QST findings and aberrant findings on functional, chemical and structural neuroimaging.
Aim 3 - To use the data from the above aims as well as other ongoing studies to develop and pilot test a more efficient and predictive self-report measure of centralization than the 2011 FM Survey Criteria, which we will refer to as the Centralized Pain Index (CPI).
Aim 4 - To explore the clinical and mechanistic features of two important subsets of centralized pain: top-down activity-independent centralization (i.e. previously termed primary FM) vs. bottom-up activity-dependent pain centralization or central sensitization (i.e. previously termed secondary FM).
Inclusion/Exclusion criteria*:
The subjects will be drawn from patients over the age of 21, who are scheduled for one of three treatments: total hip arthroplasty, carpal tunnel release, or administration of a biologic for rheumatoid arthritis (RA).
Include:
- Ability to read and speak English to allow for written informed consent, phenotyping, and patient
- reported outcomes measures;
- Willingness to participate in longitudinal follow-up (questionnaires and outcomes measures) for 6- months after their treatment (Osteoarthritis (OA), Rheumatoid arthritis (RA), and Carpal tunnel syndrome (CTS) cohorts only).
Exclude:
- Inability to provide written informed consent;
- Severe physical impairment (e.g., blindness, deafness, paraplegia);
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy, or autoimmune disorder [except the RA cohort]) (and precludes operative treatment for CTS cohort);
- Illicit drug or unreported opioid use (unreported opioid use would be considered opioid misuse or abuse and thereby exclusionary);
- Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., malignancy, psychosis, suicidal ideation; note that stable anxiety and depression are NOT exclusions);
- Pregnant;
- Liver failure (and precludes operative treatment for CTS cohort);
- Self-reported liver cirrhosis (and precludes operative treatment for CTS cohort);
- Self-reported hepatitis (and precludes operative treatment for CTS cohort);
- Uncontrolled diabetes (and precludes operative treatment for CTS cohort);
- Severe Cardiovascular disease (examples: history of myocardial infarction, unstable angina, severe coronary artery disease, congestive heart failure, or severe valvular abnormalities) that is self-reported by patient or by medical record (and precludes operative treatment for CTS cohort);
- Average daily opioid dosing of >15 mg oral morphine equivalents preoperatively (e.g., > two 5 mg oxycodone tablets/day or > three 5 mg hydrocodone tablets/day). Conversions will be made based on well-accepted conversion tools we have used previously.3,4
*There are additional Inclusion and Exclusion Criteria for different cohorts
Centralized Pain Phenotype as a Predictor of Opioid Non-Responsiveness - CPS (HUM00097718)
PI: Daniel Clauw, MD; Chad Brummett, MD
Years of funding: 5 years
Number of patients to be recruited: 200 (60 will undergo additional phenotyping and imaging)
Study goals/aims: We propose to superimpose research staff onto the clinical setting to record pain scores and standardize opioid administration to determine if FMness leads to increased pain, decreased opioid responsiveness to the same amount of pain, or both. We will also perform a prospective neuroimaging study on subsets of these individuals undergoing surgery to determine the degree to which fMRI and PET imaging studies described above can predict subsequent opioid responsiveness.
Aim 1 - Demonstrate that the baseline fibromyalgia survey score (FMness) predicts opioid responsiveness in the postoperative period in individuals with knee OA undergoing arthroplasty.
Aim 2 - Perform fMRI and PET with a µ-opioid receptor ligand prior to knee arthroplasty in a subset of Aim 1 (n = 60) patients selected to span the entire continuum of FMness to: a) predict opioid responsiveness during surgery, and b) validate that self-report FMness is closely related to fMRI evidence of measures of centralized pain (connectivity changes and hyperalgesia) as well as endogenous opioid functional measures as measured with PET.
Inclusion/Exclusion criteria:
Subjects will be drawn from patients over the age of 18 who are scheduled for primary unilateral total knee arthroplasty (TKA) at the University of Michigan. The inclusion criteria for Aims 1 and 2 will be similar, with additional exclusions for TKA (Aim 1) patients participating in the Aim 2 imaging studies.
Include - Non-Imaging (Aim 1)
- Total knee arthroplasty (TKA) patients enrolled in the Analgesic Outcome Study II (HUM#00106315)
Exclude – Non-Imaging (Aim 1)
- Taking opioids (narcotic pain medications, e.g. hydrocodone, Vicodin, Norco, morphine, methadone, fentanyl) chronically in the 3 months prior to the study visit, defined as daily use
- Any opioid (narcotic) use within 4 weeks of the first study visit
- Individuals receiving or applying for compensation or disability
- Inability to provide written informed consent
- Severe physical impairment (e.g. blindness, deafness, paraplegia)
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy)
- Known lumbar spinal stenosis (challenges/risks in performing neuraxial anesthesia)
- Illicit drug or unreported opioid use
- Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study
- Planned admission to an extended care facility or rehabilitation facility.
Include - Imaging (Aim 2)
- Total knee arthroplasty (TKA) patients enrolled in the Analgesic Outcome Study II (HUM#00106315)
- Patients over 18 but less than 76 years old (to mitigate against vascular disease leading to functional imaging abnormalities in elderly)
- Right handed
- Non-smokers (nicotine affects PET results)
- Not taking narcotic (opioid) pain medications for at least 4 weeks before the first scheduled study visit and have not taken them daily in the last 3 months No contraindications to fMRI (e.g. metal implants) or PET (e.g. exceeding allowed radiation exposure from other procedures).
- Willingness to refrain from NSAIDs and acetaminophen pain medications for 12 hours prior to dense phenotyping
- Willingness to refrain from physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to dense phenotyping (routine exercise or activity that does not lead to soreness is acceptable)
- Able to lie still on your back for 4-5 hours for PET scan.
- Fibromyalgia survey score- in order to address the underlying hypothesis, potential participants will complete the fibromyalgia survey criteria (1-page measure, approximately 2-3 min) after they discuss surgery. The questionnaire will be administered by the treating surgeon and or study staff and collected by the research team. We will recruit enough patients to satisfy the spectrum of fibromyalgia scores in four quartiles based on our previously existing data. Once a quartile is filled (e.g. 15 patients enrolled), then we will not include more people from that quartile.
Exclude - Imaging (Aim 2)
- Taking opioids (narcotic pain medications, e.g. hydrocodone, Vicodin, Norco, morphine, methadone, fentanyl) chronically in the 3 months prior to your study visit, defined as daily use
- Any opioid (narcotic) use within 4 weeks of the first study visit
- Individuals receiving or applying for compensation or disability
- Inability to provide written informed consent
- Severe physical impairment (e.g. blindness, deafness, paraplegia)
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy)
- Known lumbar spinal stenosis (challenges/risks in performing neuraxial anesthesia)
- Illicit drug or unreported opioid use
- Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study
- Planned admission to an extended care facility or rehabilitation facility.
- Subjects will be excluded from undergoing an PET scan if they would receive a total of over 5 rad to a radiosensitive organ (bone marrow, gonads, lens of the eye) or 15 rad to any other organ or to the body as a whole during a 12 month period by participating in research studies, or who are receiving medications which interfere with the study radiopharmaceuticals.
- Liver failure
- Self-reported liver cirrhosis
- Self-reported hepatitis
- Severe Cardiovascular disease (examples: hx of myocardial infarction, unstable angina, severe coronary artery disease, congestive heart failure, or severe valvular abnormalities) that are self-reported by patient or by medical record.
- Positive urine drug screen for nicotine, opioids or cannabis. Participants who test positive at screening will be allowed to rescreen after washout.
- Positive pregnancy screen or nursing during recruitment
- Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements
- Any impairment, activity or situation that in the judgement of the Principal Investigator would prevent satisfactory completion of the study
- Known severe peripheral vascular disease (self-reported)
- Known peripheral neuropathy (self-reported)
- For the visual stimulation portion of the protocol only: history of seizures or migraines.
Peripheral and Central Nervous System Mechanisms of Persistent Post-Hysterectomy Pain – MiHYST (HUM00117473)
PI: Sawsan As-Sanie, MD; Daniel Clauw, MD
Years of funding: 5 years (6/1/17-2/28/22)
Number of patients to be recruited: 500 women
Study goals/aims: Our long-term goal is to build a quantitative understanding of how peripheral and central nervous system factors independently contribute and interact to determine whether a woman will experience chronic pelvic pain (CPP), how severe that pain will be, and which women will respond to what treatments. This prospective observational study will recruit women who are scheduled to undergo hysterectomy.
Aim 1 - Demonstrate that preoperative markers of central sensitization independently predict a higher likelihood of persistent pelvic pain 12-months following hysterectomy.
Aim 2 - Demonstrate that preoperative markers indicative of peripheral sensitization independently predict a lower likelihood of persistent pelvic pain following hysterectomy.
Aim 3 - Develop an exploratory predictive model using measures of central (Aim 1) and peripheral sensitization (Aim 2), as well as additional anatomic factors (e.g. severity of anatomic pathology including endometriosis, adhesions; surgical approach), and psychosocial factors (depression, anxiety, catastrophizing, social support) to estimate the likelihood of persistent pelvic pain 12-months following hysterectomy.
Inclusion/Exclusion criteria*, **:
Include (for all subjects):
- Female scheduled for hysterectomy for benign (non-cancer) indication
- Over 21 and under 70 years of age
- Ability to read and speak English to allow for written informed consent, phenotyping, and patient reported outcome measurements
Exclude (for all subjects):
- Any chronic medical condition, psychiatric condition, or use of any medications that in the judgment of the PI would make the individual inappropriate for entry into this study or interfere with the interpretation of results. These will be considered positive if by self-report or in the medical record. (Note: Healthy controls may not have a history of persistent or recurrent mood disorder. However, CPP subjects with mood disorders such as depression or anxiety will not be excluded).
- Medical conditions that may significantly delay or interfere with postoperative recovery, or would make it unsafe for participants to take part in the study, including but not limited to: uncontrolled autoimmune/inflammatory diseases, cardiovascular or pulmonary disorders (e.g., angina, congestive heart failure, severe valvular abnormalities, COPD, chronic asthma), renal or liver disease, uncontrolled endocrine or allergic disorders (e.g., hypothyroidism, diabetes, allergic rhinitis), neurologic conditions (e.g., multiple sclerosis, prior stroke, neurological tumor, peripheral neuropathy), and malignancy (any malignancy except for localized cancers, such as treated thyroid cancer, dermatologic cancer).
- Additional major surgery which is known to significantly increase postoperative pain, morbidity, and/or recovery time planned at time of hysterectomy, such as bowel resection, orthopedic, or major breast procedure (e.g. mastectomy). Concurrent uterovaginal prolapse or incontinence procedures will be permit-ted.
- Concurrent participation in other therapeutic trials
- Pregnant and or lactating
- History of illegal drug use or substance abuse within past two years
- Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigator would prevent satisfactory completion of the study protocol.
*There are additional inclusion criteria for different cohorts
**Based on eligibility and interest in participation, each participant will be enrolled in either the “Survey-only” portion of the study, versus the “Full-study protocol”.
Transition from Acute to Chronic Pain After Thoracic Surgery – A2CPS (HUM00182709)
PI: Chad Brummett, MD
Years of funding: 3 years
Number of patients to be recruited: 1400 participants will be recruited from Michigan recruitment sites.
MCC2 (Multisite Clinical Center 2) includes University of Michigan, Henry Ford, St. Joseph Ann Arbor, Beaumont, Wayne State University, and Spectrum Health. These sites will recruit 1400 patients having thoracic surgery.
Other institutions involved:
CCC (Clinical Coordinating Center) located at University of Iowa
DIRC (Data Integration Resource Center) includes Johns Hopkins University, Texas Advanced Computing Center, and Dartmouth University.
ODGC (Omics Data Generation Centers) includes University of California San Diego, Wake Forrest University, and Pacific Northwest National Laboratory.
MCC1 (Multisite Clinical Center 1) includes Rush Medical Center, University of Chicago, University of Illinois – Chicago, and NorthShore Health System. These sites will recruit 1800 patients having knee replacement surgery
Study goals/aims: A2CPS will collect data from patients for up to 6 months after surgery. The goal is to develop a set of biomarkers or “signatures” that can predict whether a patient will transition from acute to chronic pain or be resilient. This will allow researchers to develop more individualized treatments for patients and better understand the biological bases of pain.
Aim 1 – Will use a candidate approach to examine whether putative biomarkers across multiple domains (clinical, biospecimen, psychosocial, and brain structure/function) individually predict susceptibility or resilience to the development of chronic pain 6 months after surgery.
Aim 2 – Will develop biosignatures using primary biomarkers to determine if combinations of biomarkers improve the prediction from acute to chronic pain after surgery.
Aim 3 – Will use a discover-validation approach to define novel putative biomarkers and biosignatures across multiple domains (clinical, biospecimen, psychosocial, and brain structure/function) that predict the susceptibility and resilience to development of chronic pain at 6 months post-surgery.
Inclusion/Exclusion criteria
Knee replacement cohort:
Include:
- Provision of signed and dated informed consent
- Willing to comply with all study procedures and availability for the duration of the study
- Male or female aged 18 to <85
- Individuals diagnosed with knee osteoarthritis scheduled to undergo a single primary partial or total knee replacement, conversion of a partial knee replacement, or a revision of a total knee replacement. All surgical approaches will be included for the study including robotic controlled and muscle sparing techniques.
Exclude:
- Patients undergoing surgery for an inflammatory arthritic condition such a rheumatoid arthritis or osteonecrosis
- Patients undergoing revision surgery with an infectious diagnosis involving the joint to be replaced (this will be a 2-staged procedure)
- Patients undergoing bilateral knee replacements, planned staged bilateral knee replacements within 3 months of each other, or are within 3 months of a prior contralateral knee replacement
- Patients with known contra-indications to magnetic resonance imaging (MRI)
Thoracotomy cohort:
Include:
- Provision of signed and dated informed consent
- Willing to comply with all study procedures and availability for the duration of the study
- Male or female aged 18 to <85
- Individuals scheduled for surgery using a thoracic approach at any of the participating hospitals
Exclude:
- Patients with known contra-indications to magnetic resonance imaging (MRI)
- Patients who have undergone prior thoracic surgery within 3 months
- Patients undergoing a bilateral thoracic procedure
- Patients undergoing another planned major surgery within the 6-month follow-up period
Prescribing vs. Recommending Over-The-Counter (PROTECT) Analgesics for Patients with Postoperative Pain: A Project on Non-Opioid Pain Medication Use after Discharge from Elective Surgery
PI: Mark Bicket, MD, PhD
Years of funding: NA
Number of patients to be recruited: 250 subjects between two standard of care groups – prescription group and over-the-counter group.
Study goals/aims: PROTECT is a quality improvement and survey project with the goal of evaluating the difference in self-reported consumption of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) from prescribing vs. recommending over-the-counter medication use to treat pain over 14 days following discharge from elective outpatient surgery.
Inclusion/Exclusion criteria:
Include:
- Male and female patients 18 years of age and older
- Anticipated to be prescribed and use an opioid medication to treat acute pain after elective outpatient surgery
Exclude:
- Male and female patients younger than 18 years of age
- Contraindications to taking acetaminophen or NSAIDs
- No significant analgesic medication use before surgery
- Inability to receive emails or phone calls for follow up assessment
