Use of β-hydroxy-β-methylbutyrate to Counteract Muscle Loss in Men With Prostate Cancer on Androgen Ablation

Phase 2

Completed

Conditions: Prostate Cancer

Interventions: Drug: Standard of care ADT + (HMB + arginine + glutamine)
Other: Standard of care ADT

Registration Number: NCT01607879

Lead Sponsor: Medical College of Wisconsin

Brief Summary: This is a study of HMB plus amino acids in older men with prostate cancer starting androgen deprivation therapy (ADT). The investigators hypothesize that the use of this nutritional supplementation will decrease the loss of muscle mass and strength that occurs when men start ADT.

Detailed Description: It is well established that older patients experience age-related loss of muscle mass and function (sarcopenia), presumably due to an imbalance of protein synthesis versus protein breakdown. In addition, studies have shown that men who start on ADT experience increased muscle protein breakdown and decreased synthesis. β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has been shown to slow protein breakdown. When HMB is given with arginine and lysine (which support protein synthesis) in randomized trials, researchers have shown that elderly men and women who receive this nutritional supplementation experience improvement in fat-free mass, strength, functionality and protein synthesis when compared with controls. In addition, patients with advanced cancer who experienced weight loss of at least 5% have also been shown to benefit from HMB, with supplementation resulting in a significant increase of fat-free mass when compared to controls. Thus, it seems reasonable that older men with prostate cancer starting on ADT who experience lean muscle loss as a result of aging and ADT, may achieve some benefit from supplementation with HMB as well. Use of HMB in men with prostate cancer has not been reported.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 48

Inclusion Criteria

Histologically confirmed adenocarcinoma of the prostate
Age 60 years or older
Patients with asymptomatic or minimally symptomatic prostate cancer for which they are about to start androgen deprivation therapy (ADT) per provider recommendation
- Asymptomatic or minimally symptomatic (as judged by treating physician) metastases allowed
- Men receiving ADT for localized prostate cancer are allowed
Patient able to give informed consent.

Exclusion Criteria

Patient already on ADT
Patients who are visiting clinic for a second opinion only
Patients with a diagnosis of dementia
Patients with a diagnosis of a neuromuscular disorder (i.e. multiple sclerosis)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care ADT + (HMB + AG)	Standard of care ADT + (HMB + arginine + glutamine)	Standard of care androgen deprivation therapy plus the nutritional supplement HMB + arginine + glutamine (AG)
Standard of care ADT	Standard of care ADT	Standard of care androgen deprivation therapy

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Body Composition (Lean Body Mass)	Baseline, 3 months	This measure will be the change of lean body mass from baseline reported in kilograms.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline of Dorsiflexor Muscle Size in mm^2.	Baseline and 3 months	Cross-sectional area of the dorsiflexor muscle will be measured in mm\^2 using magnetic resonance imaging. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground. One dorsiflexor muscle in one leg was analyzed per participant.
Physical Performance Measured Using the Short Physical Performance Battery (SPPB)	Baseline and 3 months	The SPPB uses Likert-style ratings for balance, walking speed, and standing test (Guralnik, 2000). Balance metric is the ability to hold three standing positions (feet side-by-side; side of the heel of one foot touching the big toe of the other foot; heel of one foot in front of and touching the toes of the other) up to 10 seconds. Inability to hold a position scores '0'. The sum of scores is the Balance Score. Scoring range is 0-4. Higher scores indicate better balance. Walking metric is time to walk 8 feet. Faster times score more points. Inability to complete the walk scores '0'. The score range is 0-4. Higher scores indicate better mobility. The Standing Test. The subject is asked to stand and sit five times as quickly as possible. Inability to complete five repetitions scores '0'. Shorter times score more points. Scoring range is 0-4. Higher scores indicate better mobility. Overall score is the sum of the scores ranging 0 to 12. Higher scores indicate better performance.
Change From Baseline in the Number of Fall Events	Baseline, 3 months	This measure will be the change in the number of reported falls from baseline (defined as the 3 months preceding the baseline visit), and the 3 month period beginning after the baseline visit and continuing through 3 months of therapy.
Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms.	Baseline and 3 months	Dorsiflexor muscle strength in kilograms will be measured with a custom lower leg ergometer. The dorsiflexor muscles at the front of the leg are responsible for lifting the ball of the foot with the heel in contact with the ground.