Starting a Testosterone and Exercise Program After Hip Injury

Purpose

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. One third of the participants will receive topical testosterone gel and a supervised exercise training program; one third will receive topical inactive gel and a supervised exercise training program; one third will receive a home exercise program. All participants will receive nutritional counseling, and calcium and vitamin D supplements.

Conditions

  • Hip Fracture
  • Frailty
  • Sarcopenia

Eligibility

Eligible Ages
Over 65 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Female 65 years and older.
  • Surgical repair of a non-pathologic fracture of the proximal femur (Including: intracapsular, intertrochanteric, and subtrochanteric fractures) with a surgical repair date that is within 6-14 weeks at screening, and within 16 weeks at randomization.
  • 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 <40 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), 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 hormone dependent neoplasia.
  • 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 levels ≥ 2.5 times above normal range.
  • Erythrocytosis with hematocrit > 51% (all sites except UCD) or ≥ 52% at UCD.
  • Severe anemia defined as Hgb < 7gm/dL.
  • Uncontrolled diabetes defined as HgbA1C > 10%.
  • Untreated or unstable thyroid disease, with serum Thyriod-stimulating Hormone (TSH) level ≥ 10 milli-international units per liter (mIU/L) or TSH level ≤ 0.4 mIU/L.
  • Site investigator's judgement that the participant would not be able to complete research procedures or interventions.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • T
  • Behavioral: Supervised exercise training
    Multicomponent exercise program focused primarily on progressive resistance exercise training
    Other names:
    • 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 names:
    • P
  • Behavioral: Supervised exercise training
    Multicomponent exercise program focused primarily on progressive resistance exercise training
    Other names:
    • EX
Other
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 names:
    • EUC
  • Behavioral: Health Education Modules
    30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise.
    Other names:
    • EUC

Recruiting Locations

University of Texas Medical Branch at Galveston (UTMB)
Galveston, Texas 77555
Contact:
Eloisa Martinez
409-266-9643
esmartin@utmb.edu

More Details

NCT ID
NCT02938923
Status
Recruiting
Sponsor
Washington University School of Medicine

Study Contact

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

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. 300 female hip fracture patients, age 65 years and older, will be enrolled from 6 clinical sites, using objective screening criteria for T deficiency (serum total testosterone level < 40 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.