Rotator Cuff TearsPhase 2ESTRCRNCT06318403
Estradiol Supplementation and Rotator Cuff Repair
A Phase 2 study testing Transdermal estrogen and Rotator Cuff Repair Surgery in people with Rotator Cuff Tears and Rotator Cuff Injuries, run by University of Utah.
Trial summary
Rotator cuff tears in the shoulder are common causes of pain and disability, often fail to heal with surgery, and tears, worse outcomes after surgery, and failure of healing are associated with estradiol deficiency. Read more about this study
- Who is it for?
- Ages 50 to 80 years, women only
- Conditions the study is for
- Rotator Cuff Tears, Rotator Cuff Injuries, Rotator Cuff Syndrome
- What is being tested?
- Transdermal estrogen and Rotator Cuff Repair Surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- No sites listed yet
- Study dates
- Mar 2028to Dec 2030
- Phase
- Phase 2
- 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 50 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A plan for a primary rotator cuff repair
- Female sex (assigned sex at birth)
- >1 cm tear width, full thickness supraspinatus/infraspinatus tear
- Post-menopausal, as defined by at least twelve months since last menses
- Age 50-80
Who cannot join
- Active infection
- Baseline serum estradiol >20 pg/mL
- Infraspinatus or supraspinatus muscle atrophy of greater than or equal to Goutallier grade 3
- Pre-operative systemic estradiol supplementation
- Medically unfit for operative intervention
- Revision surgery
Show all 16Show fewer
- Unwillingness to participate in the study, including post-operative imaging
- Inability to read or comprehend written instructions
- Prisoner
- Concomitant patch augmentation or tendon-transfer
- Breast cancer or a history of breast cancer or other estradiol-dependent neoplasia
- Liver disease as documented in the medical record
- Active venous thromboembolic disease, such as deep venous thrombosis, pulmonary embolism, a history of these conditions, or a known predisposition to these disorders (such as Protein C, protein S, or antithrombin deficiency)
- Active arterial thromboembolic disease, such as stroke, myocardiac infarction, a history of these conditions, or a known predisposition to these disorders
- Isolated subscapularis tears
- Known anaphylactic reaction or hypersensitivity to estradiol, adhesive, or transdermal patches
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Estradiol Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial
Rotator cuff tears in the shoulder are common causes of pain and disability, often fail to heal with surgery, and tears, worse outcomes after surgery, and failure of healing are associated with estradiol deficiency. In this study, post-menopausal women will be randomized to either estradiol patches or placebo patches after repair of the rotator cuff. The purpose of this study is to determine whether estradiol patches show promise in improving shoulder pain, strength, muscle volumes, and function when given with rotator cuff repair.
Read the detailed description
Injuries to the rotator cuff are among the most common musculoskeletal complaints and are increasing in incidence. Multiple studies have demonstrated that rotator cuff repair (RCR) improves outcomes for rotator cuff tears. Over 500,000 RCRs are performed in the US annually. When both surgical and non-operative treatment are included, rotator cuff injuries cost the United States over $5 billion dollars annually. After RCR, tendon healing fails to occur in >20% of patients. Improving tendon healing is thus a critical barrier to success. The field has arrived at a consensus that improving tendon biology is the key to improving tendon healing. Our prior human and animal research demonstrates that estradiol deficiency contributes to rotator cuff injuries and poor outcomes after RCR and estradiol supplementation improves RCR healing and outcomes. With this study we propose to translate these promising and compelling findings into improved clinical care of patients with rotator cuff injuries. Estradiol deficiency can be treated with hormone therapy (HT), which is widely utilized, well-tolerated, inexpensive, and FDA approved. In this study, we will conduct a phase II study of the efficacy and feasibility of HT within the setting of RCR. We hypothesize that compliance and response rates will be high while adverse events will be infrequent and equally common with estradiol patches and placebo patches. We also hypothesize that outcomes and healing will be better in the HT group than the control group. To test these hypotheses, we will conduct a randomized, placebo-controlled, double-blinded clinical trial to measure recruitment and retention rates, compliance with treatment, response to treatment of serum hormone levels, estimated effect size for power calculations, and adverse events. Postoperatively, we will evaluate validated patient-reported outcomes and tendon healing and rotator cuff muscle volumes utilizing magnetic resonance imaging. If efficacy and tolerability are demonstrated, a future large, multi-center, randomized clinical trial will be warranted. We expect these data will support the use of estradiol as a promising approach to improved healing and outcomes, supporting a future, larger, well-powered, multi-centered randomized clinical trial with longer follow-up. Such a study could improve the treatment of people with rotator cuff injuries, thereby decreasing a source of significant disability. If our hypotheses are confirmed, it would shift the paradigm on the treatment of problems with tendons and their attachments to bone throughout the body.
- Conditions
- Rotator Cuff Tears, Rotator Cuff Injuries, Rotator Cuff Syndrome, Menopause Related Conditions, Menopause
- Being tested
- Transdermal estrogen, Rotator Cuff Repair Surgery
- 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.
Transdermal estrogenDrug
All patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery.
Rotator Cuff Repair SurgeryProcedure or surgery
The operative protocol will be standardized in all patients. Both the operative protocol and post-operative rehabilitation protocol will be per our standard of care, without alteration. An arthroscopic approach will be used. In all cases a double-row rotator cuff repair using triple-loaded anchor(s) on the medial row will be used. Post-operatively all patients will be placed in a sling for six weeks. Active range of motion exercises will begin at six weeks post-operatively and strengthening will be delayed until 12 weeks post-operatively. In all phases of care our peri-operative and post-operative protocol for study patients will be similar to our current clinical practice to ensure generalizability.
| Study group | Role | What they receive |
|---|---|---|
| Transdermal estradiol patches | Experimental | All patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery. Receives: Drug: Transdermal estrogen; Procedure: Rotator Cuff Repair Surgery |
| Placebo patches | Placebo comparator | All patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery. Receives: Procedure: Rotator Cuff Repair Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
American Shoulder and Elbow Surgeons (ASES) Score
The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes ~3 minutes to complete. The validity and reliability of this score has been previously validated.
Measured: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Secondary outcomes (5)
Simple Shoulder Test (SST) Score
The SST score is a patient survey that creates a score on a 12-point scale incorporating questions regarding shoulder function. This survey contains 12 questions and takes ~3 minutes to complete. The validity and reliability of this score has been previously validated.
Measured: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Visual Analogue Score (VAS) for pain
The VAS pain score is a patient survey that creates a score on a 10 point scale incorporating a single question regarding shoulder pain. This survey takes <1 minute to complete.
Measured: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Magnetic Resonance Imaging (MRI)
MRI scans will be assessed by observers blinded to the patient's allocation. On the pre-operative MRI, pre-operative tear width, pre-operative tear retraction, cuff muscle atrophy using the Goutallier10 classification will be measured. For each patient, the post-operative MRI will be classified using the Sugaya classification, which multiple authors have demonstrated to have excellent inter-observer reliability. Sugaya grades 1, 2, and 3 will be considered "healed" and Sugaya grades 4 and 4 will be considered "re-torn". In cases of re-tear, tear width and retraction will be measured. In addition, on both pre-operative and post-operative scans rotator cuff muscle volumes will be measured, for which we have previously demonstrated to have excellent inter-observer reliability and accuracy. All post-operative MRI scans will be 3.0 tesla non-arthrogram studies in which T2 imaging will be performed in the sagittal, coronal, and axial planes.
Measured: Within 3 months pre-operatively and at 6 months (±4 weeks) post-operatively.
Strength Assessment
Rotator cuff strength, as measured with a handheld digital dynamometer (Lafayette instruments, Lafayette, IN), will be measured. Abduction strength will be measured at 30 degrees of flexion, 30 degrees of abduction, neutral rotation, and full elbow extension. External rotation strength will be measured with the arm in adduction, neutral rotation, and 90 degrees of elbow flexion. These measures will be performed by research coordinators trained to perform these assessments. We have previously demonstrated these measurements to have excellent inter-observer reliability, with abduction strength having an intra-class correlation coefficient (ICC) of 0.993 and external rotation strength having an ICC of 0.986.
Measured: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Range of motion
Range of motion will be recorded. Research personnel experienced with the use of video will measure active abduction, active forward elevation, active internal rotation in adduction, and active external rotation in adduction. This protocol has been previously used in many publications. These videos will be saved using subject numbers and then evaluated using a digital protractor by a third-party observer blinded to the subjects group. This method of range of motion measurement has been previously demonstrated to have excellent inter-observer reliability.
Measured: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2024
- Study startMar 2028 (estimated)
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (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 UtahThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Chalmers, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06318403
- Sponsor's protocol ID
- 177012
- Acronym
- ESTRCR
- Status last verified
- Mar 2026
- First submitted
- 12 Mar 2024
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The authors will plan to make their results available through multiple venues. Our plan includes the following: 1. Presentation at national scientific meetings. 2. ClinicalTrials.gov. 3. Publication in peer-reviewed literature. 4. Data sharing upon request. The PI will provide de-identified data to those who make requests for the purposes of meta-analysis. 5. Visiting Professors. 6. Website. The University of Utah regularly publishes important research results in web log ("blog") format, as does the PI on his practice website. Summaries of these results, along with links to the full results, written primarily for a general audience, will be posted as they become available. 7. Repository. Once the main findings are accepted for publication, the final dataset will be shared at https://dataverse.org. This will be performed after removal of all protected health information. 8. Progress on data sharing will be reported in our Research Progress Performance Reports annually.
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estradiol Supplementation and Rotator Cuff Repair: A Preliminary Randomized Trial
- ClinicalTrials.gov ID
- NCT06318403
- Acronym / sponsor ID
- ESTRCR / 177012
- Conditions
- Rotator Cuff Tears, Rotator Cuff Injuries, Rotator Cuff Syndrome, Menopause Related Conditions, Menopause
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Mar 2028 (estimated)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 19 Mar 2024 (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 tears in the shoulder are common causes of pain and disability, often fail to heal with surgery, and tears, worse outcomes after surgery, and failure of healing are associated with estradiol deficiency. In this study, post-menopausal women will be randomized to either estradiol patches or placebo patches after repair of the rotator cuff. The purpose of this study is to determine whether estradiol patches show promise in improving shoulder pain, strength, muscle volumes, and function when given with rotator cuff repair.
Detailed description
Injuries to the rotator cuff are among the most common musculoskeletal complaints and are increasing in incidence. Multiple studies have demonstrated that rotator cuff repair (RCR) improves outcomes for rotator cuff tears. Over 500,000 RCRs are performed in the US annually. When both surgical and non-operative treatment are included, rotator cuff injuries cost the United States over $5 billion dollars annually. After RCR, tendon healing fails to occur in >20% of patients. Improving tendon healing is thus a critical barrier to success. The field has arrived at a consensus that improving tendon biology is the key to improving tendon healing. Our prior human and animal research demonstrates that estradiol deficiency contributes to rotator cuff injuries and poor outcomes after RCR and estradiol supplementation improves RCR healing and outcomes. With this study we propose to translate these promising and compelling findings into improved clinical care of patients with rotator cuff injuries. Estradiol deficiency can be treated with hormone therapy (HT), which is widely utilized, well-tolerated, inexpensive, and FDA approved. In this study, we will conduct a phase II study of the efficacy and feasibility of HT within the setting of RCR. We hypothesize that compliance and response rates will be high while adverse events will be infrequent and equally common with estradiol patches and placebo patches. We also hypothesize that outcomes and healing will be better in the HT group than the control group. To test these hypotheses, we will conduct a randomized, placebo-controlled, double-blinded clinical trial to measure recruitment and retention rates, compliance with treatment, response to treatment of serum hormone levels, estimated effect size for power calculations, and adverse events. Postoperatively, we will evaluate validated patient-reported outcomes and tendon healing and rotator cuff muscle volumes utilizing magnetic resonance imaging. If efficacy and tolerability are demonstrated, a future large, multi-center, randomized clinical trial will be warranted. We expect these data will support the use of estradiol as a promising approach to improved healing and outcomes, supporting a future, larger, well-powered, multi-centered randomized clinical trial with longer follow-up. Such a study could improve the treatment of people with rotator cuff injuries, thereby decreasing a source of significant disability. If our hypotheses are confirmed, it would shift the paradigm on the treatment of problems with tendons and their attachments to bone throughout the body.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transdermal estradiol patches | Experimental | Drug: Transdermal estrogen, Procedure: Rotator Cuff Repair SurgeryAll patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery. |
| Placebo patches | Placebo comparator | Procedure: Rotator Cuff Repair SurgeryAll patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A plan for a primary rotator cuff repair
- Female sex (assigned sex at birth)
- >1 cm tear width, full thickness supraspinatus/infraspinatus tear
- Post-menopausal, as defined by at least twelve months since last menses
- Age 50-80
Key exclusion criteria (16 listed)
- Active infection
- Baseline serum estradiol >20 pg/mL
- Infraspinatus or supraspinatus muscle atrophy of greater than or equal to Goutallier grade 3
- Pre-operative systemic estradiol supplementation
- Medically unfit for operative intervention
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 |
|---|---|---|
| Transdermal estrogenAll patients will receive patches with identical labeling from our pharmacy, to be applied twice weekly. In the study group, these will contain 0.025 mg/day of estradiol. In the control group, these will be placebo. These will be applied twice weekly for three months beginning at the time of surgery and extending for three months after surgery. | Drug | Transdermal estradiol patches |
| Rotator Cuff Repair SurgeryThe operative protocol will be standardized in all patients. Both the operative protocol and post-operative rehabilitation protocol will be per our standard of care, without alteration. An arthroscopic approach will be used. In all cases a double-row rotator cuff repair using triple-loaded anchor(s) on the medial row will be used. Post-operatively all patients will be placed in a sling for six weeks. Active range of motion exercises will begin at six weeks post-operatively and strengthening will be delayed until 12 weeks post-operatively. In all phases of care our peri-operative and post-operative protocol for study patients will be similar to our current clinical practice to ensure generalizability. | Procedure or surgery | Placebo patches, Transdermal estradiol patches |
Primary outcome
American Shoulder and Elbow Surgeons (ASES) Score
Time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
The ASES score is a patient survey that creates a score on a 100 point scale incorporating questions regarding shoulder pain and shoulder function. This survey contains 11 questions and takes ~3 minutes to complete. The validity and reliability of this score has been previously validated.
5 secondary outcomes
Simple Shoulder Test (SST) Score
Time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Visual Analogue Score (VAS) for pain
Time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Magnetic Resonance Imaging (MRI)
Time frame: Within 3 months pre-operatively and at 6 months (±4 weeks) post-operatively.
Strength Assessment
Time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
Range of motion
Time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.
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 19 Mar 2026.
- Individual participant dataSharing planned: No. The authors will plan to make their results available through multiple venues. Our plan includes the following: 1. Presentation at national scientific meetings. 2. ClinicalTrials.gov. 3. Publication in peer-reviewed literature. 4. Data sharing upon request. The PI will provide de-identified data to those who make requests for the purposes of meta-analysis. 5. Visiting Professors. 6. Website. The University of Utah regularly publishes important research results in web log ("blog") format, as does the PI on his practice website. Summaries of these results, along with links to the full results, written primarily for a general audience, will be posted as they become available. 7. Repository. Once the main findings are accepted for publication, the final dataset will be shared at https://dataverse.org. This will be performed after removal of all protected health information. 8. Progress on data sharing will be reported in our Research Progress Performance Reports annually.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Transdermal estrogen and Rotator Cuff Repair Surgery in people with Rotator Cuff Tears and Rotator Cuff Injuries, run by University of Utah.
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 5 inclusion and 16 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: opening soon, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Peter Chalmers, MD (8015870063, chalmerspractice@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
American Shoulder and Elbow Surgeons (ASES) Score (time frame: To be collected within 3 months pre-operatively and at 6 weeks (±2 weeks), 12 weeks (±2 weeks), and 6 months (±4 weeks) post-operatively.). 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 19 Mar 2026.