Phase 3 N=83 Randomized Triple-blind Treatment

Lifestyle Intervention and Testosterone Replacement in Obese Seniors

Obesity and Hypogonadism

Bottom Line

View on ClinicalTrials.gov: NCT02367105 ↗

Enrolled (actual)

Serious AEs

2.4%

Results posted

Aug 2020

Primary outcome: Primary: Change in the Physical Performance Test — 4.6; 4.9 units on a scale — p=0.58

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Testosterone (Drug); Lifestyle Therapy (Other); Placebo (Drug)
Age: Older Adult · 65+ yrs
Sex: Male
Sponsor: VA Office of Research and Development
Primary completion: Jul 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in the Physical Performance Test	4.6; 4.9	0.58
SECONDARY Change in Endurance Capacity	2.8; 4.0	0.03 sig
SECONDARY Change in Functional Status	2.9; 3.1	.97
SECONDARY Change in Body Weight	-10.6; -9.8	0.56
SECONDARY Change in Lean Body Mass	-2.4; -1.2	0.01 sig
SECONDARY Change in Fat Mass	-8.2; -8.0	0.91
SECONDARY Change in Thigh Muscle Volume	-68; -25	0.04 sig
SECONDARY Thigh Fat Volume	-292; -262	.67
SECONDARY Change in Total Hip Bone Mineral Density	-0.013; 0.007	0.003 sig
SECONDARY Change in Lumbar Spine Bone Mineral Density	0.004; 0.007	0.69
SECONDARY Change in Muscle Strength	72; 68	0.94
SECONDARY Change in Static Balance	4.5; 5.0	0.41
SECONDARY Change in Dynamic Balance	-2.9; -3.2	0.46
SECONDARY Change in Gait Speed	8.6; 8.2	0.96
SECONDARY Change in Composite Cognitive Z-score	.273; .557	.003 sig
SECONDARY Change in Modified Mini-mental Exam	1.2; 2.1	.16
SECONDARY Stroop Interference	4.6; 3.1	0.21
SECONDARY Change in Word List Fluency	0.2; 0.9	0.41
SECONDARY Change in Ray Auditory Verbal Learning Test	3.1; 7.0	.03 sig
SECONDARY Change in Trail A	-7.7; -13.9	.03 sig
SECONDARY Change in Trail B	-10.2; -19.5	.18
SECONDARY Change in Symbol Digital Modalities Test	1.1; 2.8	0.10
SECONDARY Change in Trabecular Bone Score	0.12; .11	.65
SECONDARY Change in C-terminal Telopeptide	0.530; 0.002	0.03 sig
SECONDARY Change in N-terminal Propeptide of Type I Procollagen	-4.7; 1.5	0.04 sig
SECONDARY Change in Insulin Growth Factor-1	11.8; 16.9	0.35
SECONDARY Change in Trabecular Bone Score (Trabecular Bone Quality)	0.11; 0.12	0.65
SECONDARY Change in Levels of 25-hydroxyvitamin D	6.2; 8.3	0.27
SECONDARY Change in Parathyroid Hormone Level	12.9; 9.0	0.39
SECONDARY Change in High-sensitivity C-reactive Protein (Inflammatory Marker)	.19; .18	0.58
SECONDARY Change in Interleukin-6	-1.1; -1.0	0.90

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.

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)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02367105). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.