Rotator Cuff TearsNCT04831164
Genetic Epidemiology of Rotator Cuff Tears: The cuffGEN Study
An observational study of Rotator Cuff Tears, run by University of Michigan at 10 sites in United States.
Trial summary
Rotator cuff tear is one of the most common reasons to seek musculoskeletal care, and cuff repair is one of the fastest growing ambulatory surgery procedures. However, the etiology of cuff tears, reasons for variability treatment success, and causes of FI are poorly understood. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Rotator Cuff Tears
- What is being tested?
- NA (not an interventional study)
- How many people
- 3,500 participants
- Where
- 10 sitesUnited States
- Study dates
- 4 Mar 2021to 31 Dec 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with MRI confirmed rotator cuff tears or absence of tears will be approached to be recruited for the study.
Who may be able to join
- Aged ≥40 years to < 85 years
- Confirmed diagnosis of partial or full-thickness cuff tear on MRI (Cases) OR absence of rotator cuff tear on shoulder MRI (Controls)
- Ability and willingness to provide informed consent
- Ability to complete questionnaires in English (to maintain scientific integrity since standardized questionnaires are extensively validated in English)
Who cannot join
- Acute rotator cuff tear caused by a severe trauma
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 4 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48108
Nitin Jain, MD, 734-936-8178, jainnb@umich.edu
- Completed
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Completed
Boston Medical Center
Boston, Massachusetts, 02118
- Completed
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
- Not yet recruiting
Ohio State University
Columbus, Ohio, 43202
Gregory Cvetanovich, MD
- Completed
Parkland Health and Hospital System
Dallas, Texas, 75390
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Michael Khazzam, MD, 214-645-8917, Michael.Khazzam@utsouthwestern.edu
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Brian R Wolf, MD, Brian-wolf@uiowa.edu
- Completed
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Completed
Orthopedic Institute
Sioux Falls, South Dakota, 57117
About this study
Rotator cuff tear is one of the most common reasons to seek musculoskeletal care, and cuff repair is one of the fastest growing ambulatory surgery procedures. However, the etiology of cuff tears, reasons for variability treatment success, and causes of FI are poorly understood. A large-scale genome-wide association studies (GWAS) using imaging-verified rotator cuff tear cases and controls can address limitations in rigor of prior research and assess the genetic basis of FI and functional outcomes of cuff tear treatments.
Primary Objective: To conduct a case-control GWAS of imaging-verified symptomatic rotator cuff tear in approximately 3000-6000 individuals and replicate findings in an independent set of 3000-6000 or more imaging-verified individuals to identify common variants in several genetic loci that increase risk for rotator cuff tears.
Read more
Hypothesis: Common variants in several genetic loci increase risk for rotator cuff tears.
Secondary Objectives:
- To perform an imputed transcriptome-wide association study (TWAS) to identify and prioritize gene targets associated with rotator cuff tear by integrating GWAS summary statistics and gene-expression weights from muscle and adipose tissue available in the GTEx project. Hypothesis: Genetically predicted gene expression of multiple genes in muscle and adipose tissue are associated with rotator cuff tear.
- To identify if single nucleotide polymorphisms (SNPs) associated with rotator cuff tear and their genetic risk score (GRS) predict improved pain and function as measured by American Shoulder and Elbow Surgeons Standardized Form (ASES) and other outcome measures. Hypothesis: Select SNPs and GRS predict ASES outcome.
- To identify genetic variants associated with Fatty Infiltration (FI) in patients with cuff tears in a two stage GWAS of imaged rotator cuffs and to prioritize gene targets through an imputed-TWAS in muscle and adipose tissue.
Hypothesis: Multiple genetic variants are associated with FI and some exert their influence by altering gene expression in the muscle and adipose tissue.
Read the detailed description
Participants will complete a structured questionnaire (Appendix B) that includes medical and musculoskeletal comorbidities, Mental Health Inventory-5148, Fear Avoidance Beliefs Questionnaire (FABQ)149, and expectations of improvement from treatment. The primary patient-reported outcome (Aim 2) of our study is American Shoulder and Elbow Surgeons Standardized Form (ASES), which is a composite pain and function measure. ASES was chosen because it is widely used; is shoulder-specific and takes 2 minutes to complete; has an established minimally clinically important difference (MCID) of >9 points151; and has good psychometric properties152-155. We will use the Shoulder Pain and Disability Index (SPADI)as a secondary outcome. SPADI has good psychometric properties and an established MCID of >10 points.
We will perform a genome-wide association meta-analysis (GWAMA) in approximately 10,000 imaging-verified rotator cuff tear cases and imaging-verified controls. Discovery meta-analysis will consist of samples from cuffGEN cohort with MRI imaging (N=1,250 cases and 1,250 controls) and samples from BioVU based on MRI report-confirmed cases and controls (N ~ 2400 with equal cases and controls). Targeted variants showing some evidence of association (P < 5 x 10-6) will be replicated in an independent cohort of imaging confirmed cuff tear cases (N > 2,500) and controls (N > 2,500) from the GERA study. In addition to providing careful selection of cases via imaging confirmation, equal attention to the confirmation of lack of tears via imaging greatly reduces misclassification of cases and controls and allows for detection of effect estimates that are likely larger (away from the null). Adhering to the same stringent criteria for discovery and replication greatly improves our ability over previous studies to identify variants associated with cuff tears.
- Conditions
- Rotator Cuff Tears
- Being tested
- NA (not an interventional study)
- Keywords
- rotator cuff, shoulder, GWAS, musculoskeletal
- Medical subject headings
- Rotator Cuff Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NA (not an interventional study)Other
(not an interventional study)
| Study group | Role | What they receive |
|---|---|---|
| Case | Patients with MRI confirmed rotator cuff tears Receives: Other: NA (not an interventional study) | |
| Control | Patients without rotator cuff tears Receives: Other: NA (not an interventional study) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genome wide association meta-analysis of cases and controls
Discovery of targeted variants in MRI verified cases and controls
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2021
- Study start4 Mar 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rotator Cuff TearsStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 3,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Nitin Jain, University of Michigan
- Investigators
- Nitin Jain, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04831164
- Sponsor's protocol ID
- STU-2020-0689
- Other IDs
- 1R01AR074989-01A1
- Status last verified
- Feb 2026
- First submitted
- 31 Mar 2021
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Epidemiology of Rotator Cuff Tears: The cuffGEN Study
- ClinicalTrials.gov ID
- NCT04831164
- Acronym / sponsor ID
- STU-2020-0689
- Conditions
- Rotator Cuff Tears
- Keywords
- rotator cuff, shoulder, GWAS, musculoskeletal
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,500 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 5 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rotator cuff tear is one of the most common reasons to seek musculoskeletal care, and cuff repair is one of the fastest growing ambulatory surgery procedures. However, the etiology of cuff tears, reasons for variability treatment success, and causes of FI are poorly understood. A large-scale genome-wide association studies (GWAS) using imaging-verified rotator cuff tear cases and controls can address limitations in rigor of prior research and assess the genetic basis of FI and functional outcomes of cuff tear treatments.
Primary Objective: To conduct a case-control GWAS of imaging-verified symptomatic rotator cuff tear in approximately 3000-6000 individuals and replicate findings in an independent set of 3000-6000 or more imaging-verified individuals to identify common variants in several genetic loci that increase risk for rotator cuff tears.
Hypothesis: Common variants in several genetic loci increase risk for rotator cuff tears.
Secondary Objectives:
- To perform an imputed transcriptome-wide association study (TWAS) to identify and prioritize gene targets associated with rotator cuff tear by integrating GWAS summary statistics and gene-expression weights from muscle and adipose tissue available in the GTEx project. Hypothesis: Genetically predicted gene expression of multiple genes in muscle and adipose tissue are associated with rotator cuff tear.
- To identify if single nucleotide polymorphisms (SNPs) associated with rotator cuff tear and their genetic risk score (GRS) predict improved pain and function as measured by American Shoulder and Elbow Surgeons Standardized Form (ASES) and other outcome measures. Hypothesis: Select SNPs and GRS predict ASES outcome.
- To identify genetic variants associated with Fatty Infiltration (FI) in patients with cuff tears in a two stage GWAS of imaged rotator cuffs and to prioritize gene targets through an imputed-TWAS in muscle and adipose tissue.
Hypothesis: Multiple genetic variants are associated with FI and some exert their influence by altering gene expression in the muscle and adipose tissue.
Detailed description
Participants will complete a structured questionnaire (Appendix B) that includes medical and musculoskeletal comorbidities, Mental Health Inventory-5148, Fear Avoidance Beliefs Questionnaire (FABQ)149, and expectations of improvement from treatment. The primary patient-reported outcome (Aim 2) of our study is American Shoulder and Elbow Surgeons Standardized Form (ASES), which is a composite pain and function measure. ASES was chosen because it is widely used; is shoulder-specific and takes 2 minutes to complete; has an established minimally clinically important difference (MCID) of >9 points151; and has good psychometric properties152-155. We will use the Shoulder Pain and Disability Index (SPADI)as a secondary outcome. SPADI has good psychometric properties and an established MCID of >10 points.
We will perform a genome-wide association meta-analysis (GWAMA) in approximately 10,000 imaging-verified rotator cuff tear cases and imaging-verified controls. Discovery meta-analysis will consist of samples from cuffGEN cohort with MRI imaging (N=1,250 cases and 1,250 controls) and samples from BioVU based on MRI report-confirmed cases and controls (N ~ 2400 with equal cases and controls). Targeted variants showing some evidence of association (P < 5 x 10-6) will be replicated in an independent cohort of imaging confirmed cuff tear cases (N > 2,500) and controls (N > 2,500) from the GERA study. In addition to providing careful selection of cases via imaging confirmation, equal attention to the confirmation of lack of tears via imaging greatly reduces misclassification of cases and controls and allows for detection of effect estimates that are likely larger (away from the null). Adhering to the same stringent criteria for discovery and replication greatly improves our ability over previous studies to identify variants associated with cuff tears.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case | – | Other: NA (not an interventional study)Patients with MRI confirmed rotator cuff tears |
| Control | – | Other: NA (not an interventional study)Patients without rotator cuff tears |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with MRI confirmed rotator cuff tears or absence of tears will be approached to be recruited for the study.
Key inclusion criteria (4 listed)
- Aged ≥40 years to < 85 years
- Confirmed diagnosis of partial or full-thickness cuff tear on MRI (Cases) OR absence of rotator cuff tear on shoulder MRI (Controls)
- Ability and willingness to provide informed consent
- Ability to complete questionnaires in English (to maintain scientific integrity since standardized questionnaires are extensively validated in English)
Key exclusion criteria (1 listed)
- Acute rotator cuff tear caused by a severe trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NA (not an interventional study)(not an interventional study) | Other | Case, Control |
Primary outcome
Genome wide association meta-analysis of cases and controls
Time frame: 10 years
Discovery of targeted variants in MRI verified cases and controls
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nitin Jain, MD principal investigator
University of Michigan
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rotator Cuff Tears, run by University of Michigan at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nitin Jain, MD (734-936-8178, jainnb@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genome wide association meta-analysis of cases and controls (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.