Clinical trial NCT02938923: Starting a Testosterone and Exercise Program After Hip Injury
Official title: Combining Testosterone Therapy and Exercise to Improve Function Post Hip Fracture
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hip Fracture
Frailty
Sarcopenia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: University of Maryland, Baltimore
name: University of Colorado, Denver
name: The University of Texas Medical Branch, Galveston
name: Johns Hopkins University
name: Harvard University
name: University of Connecticut
name: University of Utah
name: University of Pittsburgh Medical Center
First posted: 2016-10-19
Enrollment: 129
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Six Minute Walk Distance
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change in Total Lean Body Mass
timeFrame: Baseline to 6 months
measure: Change in Appendicular Lean Body Mass
timeFrame: Baseline to 6 months
measure: Change in 1-repetition Maximum (1-RM) Leg Press Strength
timeFrame: Baseline to 6 months
measure: Change in Total Modified Physical Performance Test (mPPT) Score
timeFrame: Baseline to 6 months
measure: Change in Short Physical Performance Battery (SPPB) Score
timeFrame: Baseline to 6 months
measure: Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire
timeFrame: Baseline to 6 months
measure: Change in Functional Status Questionnaire (FSQ) Total Score
timeFrame: Baseline to 6 months
measure: Change in Hip Rating Questionnaire Total Score
timeFrame: Baseline to 6 months
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health
timeFrame: Baseline to 6 months
measure: Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Heath - UConn Health
state: Connecticut
city: Baltimore
country: United States
facility: University of Maryland School of Medicine/Johns Hopkins University
state: Maryland
city: Roslindale
country: United States
facility: HebrewSenior Life Harvard Medical School
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston (UTMB)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Washington University School of Medicine
name: Ellen F Binder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Kenneth B Schechtman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, Baltimore
name: Jay Magaziner, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.