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

Primary Purpose

Hip Fracture, Frailty, Sarcopenia

Status

Active

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Testosterone

Placebo gel

Supervised exercise training

Home exercise program

Health Education Modules

About this trial

This is an interventional treatment trial for Hip Fracture

Eligibility Criteria

65 Years - undefined (Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

University of Colorado, Denver
University of Connecticut Heath - UConn Health
University of Maryland School of Medicine/Johns Hopkins University
HebrewSenior Life Harvard Medical School
Washington University School of Medicine in St. Louis
University of Pittsburgh Medical Center
University of Texas Medical Branch at Galveston (UTMB)
University of Utah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Other

Arm Label

Exercise + Testosterone (EX + T)

Exercise + Placebo (EX + P)

Enhanced Usual Care (EUC)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Change in six minute walk distance at 6 months

Distance that the individual can walk on a specified track, within six minutes

Secondary Outcome Measures

Change in Total Lean Body Mass at 6 months

Total lean body mass measured by dual x-ray absorptiometry (DXA)

Change in Appendicular Lean Body Mass at 6 months

Lean body mass of the arms and legs, measures by dual x-ray absorptiometry (DXA)

Change in 1-repetition maximum (1-RM) leg press strength at 6 months

1-repetition maximum strength for leg press

Change in Total Modified Physical Performance Test (mPPT) Score at 6 months

9 objective physical performance tasks

Change in Short Physical Performance Battery (SPPB) Score at 6 months

3 objective physical performance tasks (Chair rise, Progressive Romberg, Walking speed for an 8 ft course)

Change in Older Adult Resources and Services Activities of Daily Living (ADL) Questionnaire (OARS) ADL Total Score at 6 months

Standardized self-report questions regarding performance of activities of daily living

Change in Functional Status Questionnaire (FSQ) Total Score at 6 months

Standardized self-report questions regarding performance of activities of daily living

Change in Hip Rating Questionnaire Total Score at 6 months

Standardized questions regarding quality of life and function as related to the hip fracture event

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health score at 6 months

Standardized questions regarding quality of life

Change in Bone Mineral Density (BMD) of the non-fractured proximal femur at 6 months

Bone mineral density measured by dual x-ray absorptiometry (DXA)

Full Information

NCT ID

NCT02938923

First Posted

October 14, 2016

Last Updated

February 24, 2023

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

1. Study Identification

Unique Protocol Identification Number

NCT02938923

Brief Title

Starting a Testosterone and Exercise Program After Hip Injury

Acronym

STEP-HI

Official Title

Combining Testosterone Therapy and Exercise to Improve Function Post Hip Fracture

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 15, 2017 (Actual)

Primary Completion Date

August 31, 2023 (Anticipated)

Study Completion Date

August 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Washington University School of Medicine

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hip Fracture, Frailty, Sarcopenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

129 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exercise + Testosterone (EX + T)

Arm Type

Experimental

Arm Description

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

Arm Title

Exercise + Placebo (EX + P)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Enhanced Usual Care (EUC)

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Testosterone

Other Intervention Name(s)

Intervention Description

Topical testosterone gel 1%

Intervention Type

Drug

Intervention Name(s)

Placebo gel

Other Intervention Name(s)

Intervention Description

Inactive skin gel

Intervention Type

Behavioral

Intervention Name(s)

Supervised exercise training

Other Intervention Name(s)

Intervention Description

Multicomponent exercise program focused primarily on progressive resistance exercise training

Intervention Type

Behavioral

Intervention Name(s)

Home exercise program

Other Intervention Name(s)

EUC

Intervention Description

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

Intervention Type

Behavioral

Intervention Name(s)

Health Education Modules

Other Intervention Name(s)

EUC

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in six minute walk distance at 6 months

Description

Distance that the individual can walk on a specified track, within six minutes

Time Frame

Baseline and 6 months

Secondary Outcome Measure Information:

Title

Change in Total Lean Body Mass at 6 months

Description

Total lean body mass measured by dual x-ray absorptiometry (DXA)

Time Frame

Baseline and 6 months

Title

Change in Appendicular Lean Body Mass at 6 months

Description

Lean body mass of the arms and legs, measures by dual x-ray absorptiometry (DXA)

Time Frame

Baseline and 6 months

Title

Change in 1-repetition maximum (1-RM) leg press strength at 6 months

Description

1-repetition maximum strength for leg press

Time Frame

Baseline and 6 months

Title

Change in Total Modified Physical Performance Test (mPPT) Score at 6 months

Description

9 objective physical performance tasks

Time Frame

Baseline and 6 months

Title

Change in Short Physical Performance Battery (SPPB) Score at 6 months

Description

3 objective physical performance tasks (Chair rise, Progressive Romberg, Walking speed for an 8 ft course)

Time Frame

Baseline and 6 months

Title

Change in Older Adult Resources and Services Activities of Daily Living (ADL) Questionnaire (OARS) ADL Total Score at 6 months

Description

Standardized self-report questions regarding performance of activities of daily living

Time Frame

Baseline and 6 months

Title

Change in Functional Status Questionnaire (FSQ) Total Score at 6 months

Description

Standardized self-report questions regarding performance of activities of daily living

Time Frame

Baseline and 6 months

Title

Change in Hip Rating Questionnaire Total Score at 6 months

Description

Standardized questions regarding quality of life and function as related to the hip fracture event

Time Frame

Baseline and 6 months

Title

Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health score at 6 months

Description

Standardized questions regarding quality of life

Time Frame

Baseline and 6 months

Title

Change in Bone Mineral Density (BMD) of the non-fractured proximal femur at 6 months

Description

Bone mineral density measured by dual x-ray absorptiometry (DXA)

Time Frame

Baseline and 6 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ellen F Binder, MD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kenneth B Schechtman, PhD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jay Magaziner, PhD

Organizational Affiliation

University of Maryland, Baltimore

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado, Denver

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

University of Connecticut Heath - UConn Health

City

Farmington

State/Province

Connecticut

ZIP/Postal Code

06030

Country

United States

Facility Name

University of Maryland School of Medicine/Johns Hopkins University

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

HebrewSenior Life Harvard Medical School

City

Roslindale

State/Province

Massachusetts

ZIP/Postal Code

02131

Country

United States

Facility Name

Washington University School of Medicine in St. Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15219

Country

United States

Facility Name

University of Texas Medical Branch at Galveston (UTMB)

City

Galveston

State/Province

Texas

ZIP/Postal Code

77555

Country

United States

Facility Name

University of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84108

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

36070134

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.

Results Reference

derived

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Starting a Testosterone and Exercise Program After Hip Injury

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