NCT04831164

Brief 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. 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:

  1. 1.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.
  2. 2.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.
  3. 3.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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,500

participants targeted

Target at P75+ for all trials

Timeline
69mo left

Started Mar 2021

Longer than P75 for all trials

Geographic Reach
1 country

10 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress48%
Mar 2021Dec 2031

Study Start

First participant enrolled

March 4, 2021

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

March 31, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 5, 2021

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2031

Last Updated

February 10, 2026

Status Verified

February 1, 2026

Enrollment Period

5.8 years

First QC Date

March 31, 2021

Last Update Submit

February 5, 2026

Conditions

Keywords

rotator cuffshoulderGWASmusculoskeletal

Outcome Measures

Primary Outcomes (1)

  • Genome wide association meta-analysis of cases and controls

    Discovery of targeted variants in MRI verified cases and controls

    10 years

Study Arms (2)

Case

Patients with MRI confirmed rotator cuff tears

Other: NA (not an interventional study)

Control

Patients without rotator cuff tears

Other: NA (not an interventional study)

Interventions

(not an interventional study)

CaseControl

Eligibility Criteria

Age40 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Adults with MRI confirmed rotator cuff tears or absence of tears will be approached to be recruited for the study.

You may qualify if:

  • 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)

You may not qualify if:

  • Acute rotator cuff tear caused by a severe trauma

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

COMPLETED

Boston Medical Center

Boston, Massachusetts, 02118, United States

COMPLETED

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

COMPLETED

University of Michigan

Ann Arbor, Michigan, 48108, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43202, United States

NOT YET RECRUITING

Orthopedic Institute

Sioux Falls, South Dakota, 57117, United States

COMPLETED

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

COMPLETED

Parkland Health and Hospital System

Dallas, Texas, 75390, United States

COMPLETED

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Saliva and other tissue samples including blood, urine, muscle, cartilage, bone and tendon will be collected from participants.

MeSH Terms

Conditions

Rotator Cuff Injuries

Interventions

Sodium

Condition Hierarchy (Ancestors)

RuptureWounds and InjuriesShoulder InjuriesTendon Injuries

Intervention Hierarchy (Ancestors)

Metals, AlkaliElementsInorganic ChemicalsMetals, LightMetals

Study Officials

  • Nitin Jain, MD

    University of Michigan

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nitin Jain, MD

CONTACT

Sravanthi Kaza, MS

CONTACT

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Physical Medicine & Rehabilitation, and Orthopaedics

Study Record Dates

First Submitted

March 31, 2021

First Posted

April 5, 2021

Study Start

March 4, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2031

Last Updated

February 10, 2026

Record last verified: 2026-02

Locations