Starting a Testosterone and Exercise Program After Hip Injury

NCT ID: NCT02938923

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-05
• Study Completion Date: 2023-11-06

Brief Summary

This study is a randomized controlled double-blinded multi-center clinical trial enrolling female hip fracture patients who are 65 and older. It will compare the effects of six months of supervised exercise training combined with daily topical testosterone gel, to six months of supervised exercise and inactive gel, and to Enhanced Usual Care. The randomization protocol is that for every nine participants randomized, 4 will be assigned to the topical testosterone gel and supervised exercise training group; 4 will be assigned to topical inactive gel and supervised exercise training group; and 1 will be assigned to the enhanced usual care group. All participants will receive nutritional counseling, and calcium and vitamin D supplements.

Detailed Description

Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. A clinically important functional decline and failure to recover following a hip fracture has been documented as late as a year after the fracture, even among women who were functioning at high levels before the event. Age-associated androgen deficiency in women contributes to deficits in muscle mass, strength and power that are common in this patient population before the fracture, and are exacerbated afterward. A pilot study of testosterone (T) supplementation in elderly female hip fracture patients has demonstrated the feasibility of T treatment in this population, and showed gains in lean body mass (LBM) and muscle strength with active drug, compared to placebo. The benefits of exercise in restoring muscle strength and physical function after a hip fracture have been documented. However, it remains unclear whether T treatment can augment the effects of exercise on mobility and patient-reported function after hip fracture.

The STEP-HI study is a 3-group, multi-center, randomized, placebo-controlled, double-blinded, parallel group clinical trial in older female hip fracture patients. Between 120 and 168 female hip fracture patients, age 65 years and older, will be randomized from multiple clinical sites in the USA, using objective screening criteria for T deficiency (serum total testosterone level < 60 ng/dL) and physical frailty (Modified Physical Performance Test (PPT) Score of 12-28). The primary study aim is to compare supervised exercise training (EX) with inactive (placebo) gel (EX+P) and EX combined with T therapy (EX+T), to ascertain the incremental impact of adding T to EX in older adult women with a recent hip fracture. The study team will carefully monitor testosterone levels, adverse events, biochemical parameters, and factors related to adherence to the interventions.

Information from this study has the potential to alter treatment of hip fracture in older women, a problem that contributes to significant morbidity and mortality, and has a large public health impact. The STEP-HI study is highly aligned with NIA's mission of identifying interventions that target common geriatric conditions and improve treatment options for older adults with multiple morbidities or risk factors.

Conditions

Hip Fracture; Frailty; Sarcopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Exercise + Testosterone (EX + T)

Supervised exercise training 2 times per week and topical testosterone 1% gel (12.5 mg per pump depression) daily, both for six months duration.

Group Type: EXPERIMENTAL

Testosterone

Intervention Type: DRUG

Topical testosterone gel 1%

Supervised exercise training

Intervention Type: BEHAVIORAL

Multicomponent exercise program focused primarily on progressive resistance exercise training

Exercise + Placebo (EX + P)

Supervised exercise training 2 times per week and placebo gel daily, both for six months duration.

Group Type: PLACEBO_COMPARATOR

Placebo gel

Intervention Type: DRUG

Inactive skin gel

Supervised exercise training

Intervention Type: BEHAVIORAL

Multicomponent exercise program focused primarily on progressive resistance exercise training

Enhanced Usual Care (EUC)

Home exercise program 3 times per week and monthly health education modules, both for six months duration.

Group Type: OTHER

Home exercise program

Intervention Type: BEHAVIORAL

Flexibility exercises performed at home 3 times per week and reviewed by study staff once a month.

Health Education Modules

Intervention Type: BEHAVIORAL

30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise.

Interventions

Testosterone

Topical testosterone gel 1%

Intervention Type: DRUG

Placebo gel

Inactive skin gel

Intervention Type: DRUG

Supervised exercise training

Multicomponent exercise program focused primarily on progressive resistance exercise training

Intervention Type: BEHAVIORAL

Home exercise program

Flexibility exercises performed at home 3 times per week and reviewed by study staff once a month.

Intervention Type: BEHAVIORAL

Health Education Modules

30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise.

Intervention Type: BEHAVIORAL

Other Intervention Names

T; P; EX; EUC; EUC

Eligibility Criteria

Inclusion Criteria

• Female 65 years and older.
• Surgical repair of a non-pathologic fracture of the proximal femur (Including: femoral neck or intracapsular, intertrochanteric, and subtrochanteric fractures) with a surgical repair date that is within 24 weeks at randomization. If a revision of such a fracture is performed due to failure of the repair, that surgery revision date may be used to calculate the time frame for the screening and randomization dates.
• Community-dwelling or in assisted living prior to the hip fracture event.
• Functional impairment at the time of screening, defined as a modified Physical Performance Score (mPPT) of 12-28.
• Serum total testosterone level <60 ng/dL.

Exclusion Criteria

• Cognitive impairment or dementia of severity sufficient to interfere with ability to fully participate in the study or provide one's own informed consent, or a score of 11 or greater on the Short Blessed Test of Orientation, Memory and Concentration.
• Residence too far from research center (specific distance to be determined by each site) or planned travel greater than 2 weeks within the next 9 months.
• Anticipated to be permanently living in a nursing home at the time of randomization.
• Use of progestin or androgen containing compound within the previous 6 months.
• Treatment with systemic corticosteroids (daily dose > 5 mg prednisone or equivalent) for at least 90 days within the previous 12 months.
• Visual or hearing impairments that interfere with following directions for research procedures.
• Active or unstable cardiopulmonary disease (recent myocardial infarction, unstable angina, class III or IV Congestive Heart Failure) within prior 6 months, which would limit full participation in the study.
• Respiratory disease requiring chronic continuous oxygen therapy, or oxygen therapy during walking or exercise, which would limit full participation in this study.
• History of idiopathic deep venous thrombosis or pulmonary embolus (i.e., not related to period or immobilization or surgery), any pulmonary embolus less than 12 weeks prior to the first screening visit, recurrent or multiple venous thrombi; history of a hypercoagulable state such as Factor V Leiden thrombophilia.
• Musculoskeletal or neurological conditions that limit participation in this study, could be made worse by exercise training, or not expected to improve with exercise.
• Lower extremity amputation other than toes.
• Severe lower extremity pain or ulceration that could limit full participation in this study.
• History of: a) Breast, ovarian, endometrial or cervical cancer with diagnosis within the previous 10 years; b) Breast, ovarian, endometrial, or cervical cancer of Stage 2 or higher.
• History of HIV or active viral hepatitis.
• End Stage Renal Disease on dialysis or Glomerular Filtration Rate (GFR)<15 ml/min.
• Allergy to gel components.
• Recent history of alcohol or substance abuse, or current alcohol intake of ≥ 10 drinks/week.
• Planned joint surgery during the intervention period.
• Participation in another research study that in the site investigator's judgement could interfere or conflict with STEP-HI research assessments or interventions.
• Current use of aldactone, flutamide or leflunomide.
• Geriatric Depression Scale (GDS) score ≥ 12 at the screening assessment.
• Uncontrolled hypertension, defined as a systolic BP > 160 mmHg or diastolic BP > 95 mmHg, on at least two occasions.
• Elevated liver transaminase or alkaline phosphatase levels ≥ 2.5 times above normal range.
• Erythrocytosis defined as hematocrit > 51% (all sites but University of Utah) or ≥ 52% at University of Colorado - Denver and University of Utah sites.
• Severe anemia defined as Hgb < 7gm/dL.
• Uncontrolled diabetes defined as HgbA1C > 10%.
• Untreated or unstable thyroid disease, with serum Thyroid-stimulating Hormone (TSH) level ≥ 10 milli-international units per liter (mIU/L) or TSH level ≤ 0.4 mIU/L. Levels outside of the given range require site physician documentation addressing treatment or absence of thyroid disease and approval by the Central Coordinating Center (CCC).
• Site investigator's judgement that the participant would not be able to complete research procedures or interventions.

• Minimum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Harvard University

OTHER

Sponsor Role: collaborator

University of Connecticut

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Ellen F. Binder, MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ellen F Binder, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Kenneth B Schechtman, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Jay Magaziner, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Colorado, Denver

Aurora, Colorado, United States

University of Connecticut Heath - UConn Health

Farmington, Connecticut, United States

University of Maryland School of Medicine/Johns Hopkins University

Baltimore, Maryland, United States

HebrewSenior Life Harvard Medical School

Roslindale, Massachusetts, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Texas Medical Branch at Galveston (UTMB)

Galveston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Binder EF, Christensen JC, Stevens-Lapsley J, Bartley J, Berry SD, Dobs AS, Fortinsky RH, Hildreth KL, Kiel DP, Kuchel GA, Marcus RL, McDonough CM, Orwig D, Sinacore DR, Schwartz RS, Volpi E, Magaziner J, Schechtman KB. A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic. Contemp Clin Trials. 2021 May;104:106356. doi: 10.1016/j.cct.2021.106356. Epub 2021 Mar 11.

Reference Type: BACKGROUND

PMID: 33716173 (View on PubMed)

Binder EF, Bartley JM, Berry SD, Dore PM, Fisher SR, Fortinsky RH, Guild C, Kiel DP, Kuchel GA, Marcus RL, McDonough CM, Monroe KM, Orwig DL, Paluch RA, Reeds D, Stevens-Lapsley J, Volpi E, Schechtman KB, Magaziner JS. Combining Exercise Training and Testosterone Therapy in Older Women After Hip Fracture: The STEP-HI Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e2510512. doi: 10.1001/jamanetworkopen.2025.10512.

Reference Type: DERIVED

PMID: 40372752 (View on PubMed)

Fairhall NJ, Dyer SM, Mak JC, Diong J, Kwok WS, Sherrington C. Interventions for improving mobility after hip fracture surgery in adults. Cochrane Database Syst Rev. 2022 Sep 7;9(9):CD001704. doi: 10.1002/14651858.CD001704.pub5.

Reference Type: DERIVED

PMID: 36070134 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

201609077

Identifier Type: OTHER

Identifier Source: secondary_id

R01AG051647

Identifier Type: NIH

Identifier Source: org_study_id

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