Starting a Testosterone and Exercise Program After Hip Injury

NCT02938923 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: R01AG051647201609077
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 8

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.

Conditions

Hip Fracture; Frailty; Sarcopenia

Outcome Measures

Primary Outcomes (1)

• Change in Six Minute Walk Distance

  Walking endurance was measured using a 6-Minute Walk Distance. Participants were asked to walk back and forth on a measured path marked clearly at both ends for turning purposes, while being told when each minute has passed, and receiving verbal encouragement every 60 seconds. Total distance was measured in meters with higher distances equating to higher walking endurance. Each individual participant distance from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in walking distance. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.

  Baseline to 6 months

Secondary Outcomes (10)

• Change in Total Lean Body Mass

  Baseline to 6 months

• Change in Appendicular Lean Body Mass

  Baseline to 6 months

• Change in 1-repetition Maximum (1-RM) Leg Press Strength

  Baseline to 6 months

• Change in Total Modified Physical Performance Test (mPPT) Score

  Baseline to 6 months

• Change in Short Physical Performance Battery (SPPB) Score

  Baseline to 6 months

Study Arms (3)

Exercise + Testosterone (EX + T)

EXPERIMENTAL

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

Drug: Testosterone; Behavioral: Supervised exercise training

Exercise + Placebo (EX + P)

PLACEBO COMPARATOR

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

Drug: Placebo gel; Behavioral: Supervised exercise training

Enhanced Usual Care (EUC)

OTHER

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

Behavioral: Home exercise program; Behavioral: Health Education Modules

Interventions

Testosterone DRUG

Topical testosterone gel 1%

Also known as: T

Exercise + Testosterone (EX + T)

Placebo gel DRUG

Inactive skin gel

Also known as: P

Exercise + Placebo (EX + P)

Supervised exercise training BEHAVIORAL

Multicomponent exercise program focused primarily on progressive resistance exercise training

Also known as: EX

Exercise + Placebo (EX + P); Exercise + Testosterone (EX + T)

Home exercise program BEHAVIORAL

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

Also known as: EUC

Enhanced Usual Care (EUC)

Health Education Modules BEHAVIORAL

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

Also known as: EUC

Enhanced Usual Care (EUC)

Eligibility Criteria

• Age: 65 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• University of Maryland, Baltimore: collaborator
• University of Colorado, Denver: collaborator
• The University of Texas Medical Branch, Galveston: collaborator
• Johns Hopkins University: collaborator
• Harvard University: collaborator
• University of Connecticut: collaborator
• University of Utah: collaborator
• University of Pittsburgh Medical Center: collaborator

Study Sites (8)

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

University of Connecticut Heath - UConn Health

Farmington, Connecticut, 06030, United States

Location

University of Maryland School of Medicine/Johns Hopkins University

Baltimore, Maryland, 21201, United States

Location

HebrewSenior Life Harvard Medical School

Roslindale, Massachusetts, 02131, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15219, United States

Location

University of Texas Medical Branch at Galveston (UTMB)

Galveston, Texas, 77555, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (4)

• 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.

  PMID: 33716173 BACKGROUND

• Earp JE, Zhao S, Xu F, Kuo CL, Bartley JM, Fortinsky RH, Kositsawat J, Rehbein CO, Binder EF, Stevens-Lapsley J, Kuchel GA. Testosterone therapy effects adipose distribution in older females post hip-fracture: The STEP-HI study. Obes Pillars. 2026 Jan 12;17:100247. doi: 10.1016/j.obpill.2026.100247. eCollection 2026 Mar.

  PMID: 41624165 DERIVED

• 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.

  PMID: 40372752 DERIVED

• 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.

  PMID: 36070134 DERIVED

MeSH Terms

Conditions

Hip Fractures; Frailty; Sarcopenia

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Ellen F. Binder, Professor of Medicine and Occupational Therapy
• Organization: Washington University in St. Louis School of Medicine

ebinder@wustl.edu

314-286-2707

Study Officials

• Ellen F Binder, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Kenneth B Schechtman, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Jay Magaziner, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, and study staff conducting the interventions will be aware of the exercise group assignment. A Blinded Outcomes Assessor will be masked to study group assignment. Only the study pharmacist, an unblinded study physician, and Data Coordinating Center staff will be unblinded to gel treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 19, 2016
• Study Start: March 5, 2019
• Primary Completion: August 31, 2023
• Study Completion: November 6, 2023
• Last Updated: February 4, 2025
• Results First Posted: February 4, 2025

Record last verified: 2025-01

Locations

US (8)