Lifestyle Intervention and Testosterone Replacement in Obese Seniors
Condition: Obesity and Hypogonadism
MeSH terms: Hypogonadism
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Testosterone; Lifestyle Therapy; Placebo
Intervention type(s): Drug; Other; Drug
Intervention description(s): Daily testosterone gel applied once daily in the morning to intact skin; Weekly behavioral diet to induce ~10% weight loss in combination with supervised aerobic and exercise training three times a week; Placebo gel for testosterone
Intervention MeSH terms: Testosterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obesity; Hypogonadism; Frailty