Lifestyle Intervention and Testosterone Replacement in Obese Seniors

NCT ID: NCT02367105

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-01
• Study Completion Date: 2019-12-31

Brief Summary

The prevalence of obesity in Veterans is greater than in the general population, and even more so among users of the VA Health Care System. In addition, the population of obese older Veterans is rapidly increasing as more baby boomers become senior citizens. In older Veterans, obesity exacerbates the age- related decline in physical function and causes frailty which predisposes to admission to a VA chronic care facility. However, the optimal clinical approach to obesity in older adults is controversial because of the concern that weight loss therapy could be harmful by aggravating the age-related loss of muscle mass and bone mass. In fact, the MOVE (Managing Overweight/Obese Veterans) program does not have any guidelines for eligible Veterans if they are 70 or older. It is possible that the addition of testosterone replacement to lifestyle therapy will preserve muscle mass and bone mass and reverse frailty in obese older Veterans and thus prevent their loss of independence and decrease demand for VA health care services.

Detailed Description

Obesity is not only highly prevalent among Americans, but even more so among Veterans using VA medical facilities. Failure to assist Veterans in managing weight and sedentary lifestyle affects current treatment and increases future demand for VA health care services. Decreased muscle mass with aging and the need to carry extra mass due to obesity make it particularly difficult for obese older Veterans to function independently and results in frailty leading to increased nursing home admissions and increased morbidity and mortality. Data from preliminary studies showed that lifestyle therapy resulting in weight loss in this understudied population improves physical function and ameliorates frailty. However, this improvement in physical function is modest at best and most obese older adults remain physically frail. More importantly, there are concerns that lifestyle therapy may exacerbate underlying sarcopenia and osteopenia from weight loss- induced loss of lean body mass and bone mineral density (BMD). As a result, most geriatricians are reluctant to recommend lifestyle therapy that includes weight loss in obese frail elderly patients although the combination of weight loss and exercise is recommended as part of standard care for obese patients in general. Thus, it is not surprising that among Veterans, the MOVE (Managing Overweight/Obese Veterans) program does not have any guidelines for eligible Veterans if they are 70 or older. In addition to overeating and lack of exercise, age-related decline in anabolic hormone (i.e. testosterone) may contribute to sarcopenia and osteopenia, which in turn is exacerbated by obesity. Indeed, preliminary studies discovered that obese older men had markedly low levels of serum testosterone at baseline which remained low throughout the duration of lifestyle therapy. Because testosterone replacement therapy has been shown to increase muscle mass and BMD, it is therefore likely that concomitant testosterone replacement during lifestyle therapy in obese older adults would preserve lean body mass and BMD, and reverse frailty. Accordingly, the optimal management to the problem of sarcopenic obesity and frailty might require a comprehensive approach of a combination of lifestyle intervention and the correction of anabolic hormone deficiency. Therefore, the primary goal of this proposal is to conduct a randomized, comparative efficacy, double-blind, placebo-controlled (for testosterone) trial of the effects of 1) lifestyle therapy (1% diet-induced weight loss and exercise training) + testosterone replacement therapy versus 2) lifestyle therapy without testosterone replacement (testosterone placebo) in obese (BMI e 30 kg/m2) older (age e 65 yrs) male Veterans. The investigators hypothesize that 1) lifestyle therapy + testosterone replacement will cause a greater improvement in physical function than lifestyle therapy without concomitant testosterone replacement; 2) lifestyle therapy + testosterone replacement will cause a greater preservation of fat-free mass and thigh muscle volume than lifestyle therapy without testosterone replacement, 3) lifestyle therapy + testosterone replacement will cause a greater preservation in BMD and bone quality than lifestyle therapy without testosterone replacement, and 4) lifestyle therapy + testosterone replacement will cause a greater reduction in intramuscular proinflammatory cytokines than lifestyle therapy without testosterone replacement. The overarching hypothesis across aims is that a multifactorial intervention by means of lifestyle therapy plus testosterone replacement will be the most effective approach for reversing sarcopenic obesity and frailty in obese older male adults, as mediated by their additive effects in suppressing chronic inflammation, and stimulating muscle and bone anabolism. Obesity in older adults, including many aging Veterans, is a major public health problem. In fact, the public health success that has occurred in recent years could be in danger if lifestyles of older adults are neglected. The novel health outcomes and mechanistic-based data generated from this proposed randomized clinical trial (RCT) will have important ramifications for the standard of care for this rapidly increasing segment of the aging Veteran population.

Conditions

Obesity and Hypogonadism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Testosterone plus Lifestyle Therapy

Testosterone replacement in combination with behavioral diet to induce \~10% weight loss + supervised aerobic and exercise training

Group Type: ACTIVE_COMPARATOR

Testosterone

Intervention Type: DRUG

Daily testosterone gel applied once daily in the morning to intact skin

Lifestyle Therapy

Intervention Type: OTHER

Weekly behavioral diet to induce \~10% weight loss in combination with supervised aerobic and exercise training three times a week

Placebo plus Lifestyle Therapy

Placebo in combination with behavioral diet to induce \~10% weight loss and supervised aerobic and exercise training

Group Type: PLACEBO_COMPARATOR

Lifestyle Therapy

Intervention Type: OTHER

Weekly behavioral diet to induce \~10% weight loss in combination with supervised aerobic and exercise training three times a week

Placebo

Intervention Type: DRUG

Placebo gel for testosterone

Interventions

Testosterone

Daily testosterone gel applied once daily in the morning to intact skin

Intervention Type: DRUG

Lifestyle Therapy

Weekly behavioral diet to induce \~10% weight loss in combination with supervised aerobic and exercise training three times a week

Intervention Type: OTHER

Placebo

Placebo gel for testosterone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects will be

• older (65-85 yr)
• obese (BMI 30 kg/m2 or greater) Veteran men with low testosterone (less than 300 mg/dL) as defined by the Endocrine Society
• mild to moderately frail
• must have stable weight (~not less than or more than 2 kg) during the last 6 months
• sedentary (regular exercise less than 1 h/week or less than 2x/week for the last 6 months)

Exclusion Criteria

• Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, in which exercise or dietary restriction are contraindicated, or that would interfere with interpretation of results.
• Examples include, but are not limited to:

• cardiopulmonary disease (e.g. recent myocardial infarction (MI), unstable angina, stroke etc) or unstable disease (e.g. CHF)
• severe orthopedic/musculoskeletal or neuromuscular impairments
• visual or hearing impairments
• cognitive impairment (Mini Mental State Exam Score less than 24)
• current use of bone active drugs
• uncontrolled diabetes (i.e. fasting blood glucose more than 140 mg/dl and/or HbA1c greater than 9.5%).
• Any contraindications to testosterone supplementation

• history of prostate or breast cancer
• history of testicular disease
• untreated sleep apnea
• hematocrit more than 50%
• prostate-related findings of palpable nodule on exam, a serum PSA of 4.0 ng/ml or greater
• International Prostate Symptom Sore more than 19
• history of venous thromboembolism
• Osteoporosis or a BMD T-score of -2.5 in the lumbar spine or total hip as well as those patients with a history of osteoporosis-related fracture (spine, hip, or wrist)

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Michael E. DeBakey VA Medical Center

FED

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Biomedical Research Institute of New Mexico

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dennis T Villareal, MD

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center, Houston, TX

Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Countries

United States

References

Gregori G, Celli A, Barnouin Y, Paudyal A, Armamento-Villareal R, Napoli N, Qualls C, Villareal DT. Cognitive response to testosterone replacement added to intensive lifestyle intervention in older men with obesity and hypogonadism: prespecified secondary analyses of a randomized clinical trial. Am J Clin Nutr. 2021 Nov 8;114(5):1590-1599. doi: 10.1093/ajcn/nqab253.

Reference Type: DERIVED

PMID: 34375393 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CX000906

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ENDA-034-12F

Identifier Type: -

Identifier Source: org_study_id