Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI)

• ClinicalTrials.gov Identifier: NCT02938923
• Recruitment Status: Recruiting
• First Posted: October 19, 2016
• Last Update Posted: June 2, 2022
• Sponsor: Washington University School of Medicine
• Collaborators: University of Maryland, Baltimore; University of Colorado, Denver; The University of Texas Medical Branch, Galveston; Johns Hopkins University; Harvard University; University of Connecticut; University of Utah; University of Pittsburgh Medical Center
• Information provided by (Responsible Party): Ellen F. Binder, MD, Washington University School of Medicine

Study Description

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. Out of nine participants, 4 will receive topical testosterone gel and a supervised exercise training program; 4 will receive topical inactive gel and a supervised exercise training program; and 1 will receive a home exercise program. All participants will receive nutritional counseling, and calcium and vitamin D supplements.

Condition or disease	Intervention/treatment	Phase
Hip Fracture; Frailty; Sarcopenia	Drug: Testosterone; Drug: Placebo gel; Behavioral: Supervised exercise training; Behavioral: Home exercise program; Behavioral: Health Education Modules	Phase 3

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 enrolled from multiple clinical sites, 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 trial will compare the effects of Enhanced Usual Care with home exercises and no gel treatment (EUC), 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: 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.
• Primary Purpose: Treatment
• Official Title: Combining Testosterone Therapy and Exercise to Improve Function Post Hip Fracture
• Actual Study Start Date: September 15, 2017
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Testosterone; Topical testosterone gel 1%; Other Name: T; Behavioral: Supervised exercise training; Multicomponent exercise program focused primarily on progressive resistance exercise training; Other Name: EX
Placebo Comparator: Exercise + Placebo (EX + P); Supervised exercise training 2 times per week and placebo gel daily, both for six months duration.	Drug: Placebo gel; Inactive skin gel; Other Name: P; Behavioral: Supervised exercise training; Multicomponent exercise program focused primarily on progressive resistance exercise training; Other Name: EX
Enhanced Usual Care (EUC); Home exercise program 3 times per week and monthly health education modules, both for six months duration.	Behavioral: Home exercise program; Flexibility exercises performed at home 3 times per week and reviewed by study staff once a month.; Other Name: EUC; Behavioral: Health Education Modules; 30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise.; Other Name: EUC

Outcome Measures

Primary Outcome Measures :

1. Change in six minute walk distance at 6 months [ Time Frame: Baseline and 6 months ]
   Distance that the individual can walk on a specified track, within six minutes

Secondary Outcome Measures :

1. Change in Total Lean Body Mass at 6 months [ Time Frame: Baseline and 6 months ]
   Total lean body mass measured by dual x-ray absorptiometry (DXA)
2. Change in Appendicular Lean Body Mass at 6 months [ Time Frame: Baseline and 6 months ]
   Lean body mass of the arms and legs, measures by dual x-ray absorptiometry (DXA)
3. Change in 1-repetition maximum (1-RM) leg press strength at 6 months [ Time Frame: Baseline and 6 months ]
   1-repetition maximum strength for leg press
4. Change in Total Modified Physical Performance Test (mPPT) Score at 6 months [ Time Frame: Baseline and 6 months ]
   9 objective physical performance tasks
5. Change in Short Physical Performance Battery (SPPB) Score at 6 months [ Time Frame: Baseline and 6 months ]
   3 objective physical performance tasks (Chair rise, Progressive Romberg, Walking speed for an 8 ft course)
6. Change in Older Adult Resources and Services Activities of Daily Living (ADL) Questionnaire (OARS) ADL Total Score at 6 months [ Time Frame: Baseline and 6 months ]
   Standardized self-report questions regarding performance of activities of daily living
7. Change in Functional Status Questionnaire (FSQ) Total Score at 6 months [ Time Frame: Baseline and 6 months ]
   Standardized self-report questions regarding performance of activities of daily living
8. Change in Hip Rating Questionnaire Total Score at 6 months [ Time Frame: Baseline and 6 months ]
   Standardized questions regarding quality of life and function as related to the hip fracture event
9. Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health score at 6 months [ Time Frame: Baseline and 6 months ]
   Standardized questions regarding quality of life
10. Change in Bone Mineral Density (BMD) of the non-fractured proximal femur at 6 months [ Time Frame: Baseline and 6 months ]
    Bone mineral density measured by dual x-ray absorptiometry (DXA)

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Ellen F Binder, MD; 314-286-2707; ebinder@wustl.edu

Contact: Kelly M Monroe, MSW; 314-273-1160; monroek@wustl.edu

Locations

United States, Colorado

University of Colorado, Denver; Terminated

Aurora, Colorado, United States, 80045

United States, Connecticut

University of Connecticut Heath - UConn Health; Recruiting

Farmington, Connecticut, United States, 06030

Contact: Heather McAbee-Sevick 806-679-6115 mcabeesevick@uchc.edu

Principal Investigator: George Kuchel, MD

Sub-Investigator: Richard Fortinsky, PhD

Sub-Investigator: Jenna Bartley, PhD

United States, Maryland

University of Maryland School of Medicine/Johns Hopkins University; Terminated

Baltimore, Maryland, United States, 21201

United States, Massachusetts

HebrewSenior Life Harvard Medical School; Recruiting

Roslindale, Massachusetts, United States, 02131

Contact: Evelyn O'Neill 617-971-5347 oneill@hsl.harvard.edu

Contact: Sarah Berry, MD 617-971-5355

Principal Investigator: Douglas P. Kiel, MD

Sub-Investigator: Sarah Berry, MD

United States, Missouri

Washington University School of Medicine in St. Louis; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Amy Young 314-273-0338 amyyoung@wustl.edu

Principal Investigator: Ellen Binder, MD

United States, Pennsylvania

University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15219

Contact: Christine McDonough 412-383-4603 CMM295@pitt.edu

Principal Investigator: Christine McDonough, PT, PhD

United States, Texas

University of Texas Medical Branch at Galveston (UTMB); Recruiting

Galveston, Texas, United States, 77555

Contact: Eloisa Martinez 409-266-9643 esmartin@utmb.edu

Contact: Eloisa

Principal Investigator: Elena Volpi, MD, PhD

United States, Utah

University of Utah; Recruiting

Salt Lake City, Utah, United States, 84108

Contact: Nick Knight 480-298-5836 Nick.Knight@utah.edu

Principal Investigator: Robin Marcus, PT, PhD

Sponsors and Collaborators

Washington University School of Medicine

University of Maryland, Baltimore

University of Colorado, Denver

The University of Texas Medical Branch, Galveston

Johns Hopkins University

Harvard University

University of Connecticut

University of Utah

University of Pittsburgh Medical Center

Investigators

• Principal Investigator: 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

More Information

• Responsible Party: Ellen F. Binder, MD, Professor of Medicine, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02938923
• Other Study ID Numbers: R01AG051647 ( U.S. NIH Grant/Contract ); 201609077 ( Other Identifier: Washington University HRPO )
• First Posted: October 19, 2016
• Last Update Posted: June 2, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sarcopenia; Frailty; Hip Fractures; Fractures, Bone; Wounds and Injuries; Pathologic Processes; Femoral Fractures; Hip Injuries; Leg Injuries; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs