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

Use of β-hydroxy-β-methylbutyrate to Counteract Loss of Muscle Mass and Strength in Older Men With Prostate Cancer Started on Androgen Deprivation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Standard of care ADT + (HMB + arginine + glutamine); Other: Standard of care 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate
2. Age 60 years or older

3. 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
4. Patient able to give informed consent.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard of care ADT + (HMB + AG); Standard of care androgen deprivation therapy plus the nutritional supplement HMB + arginine + glutamine (AG)	Drug: Standard of care ADT + (HMB + arginine + glutamine); 1 packet of HMB+arginine+glutamine contains 1.5 g of the amino acid metabolite HMB + 7 g arginine and 7 g glutamine. Take one packet twice daily for 3 months; Other Names: Juven
Active Comparator: Standard of care ADT; Standard of care androgen deprivation therapy	Other: Standard of care ADT; Patient will receive standard of care androgen deprivation therapy (ADT) alone; Other Names: Standard of care androgen deprivation therapy (ADT)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Dorsiflexor Muscle Size in mm^2.	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.	Baseline and 3 months
Change From Baseline in Strength of the Dorsiflexor Muscle in Kilograms.	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.	Baseline and 3 months
Physical Performance Measured Using the Short Physical Performance Battery (SPPB)	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.	Baseline and 3 months
Change From Baseline in the Number of Fall Events	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.	Baseline, 3 months

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Kathryn Bylow, MD, Medical College of Wisconsin

Publications and helpful links

General Publications

• Guralnik JM, Ferrucci L, Pieper CF, Leveille SG, Markides KS, Ostir GV, Studenski S, Berkman LF, Wallace RB. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000 Apr;55(4):M221-31. doi: 10.1093/gerona/55.4.m221.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): February 16, 2021

Study Registration Dates

• First Submitted: April 20, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (Estimated): May 30, 2012

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Elderly; Prostate Cancer; Androgen Deprivation Therapy; Geriatric; Men; Nutritional supplementation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: 00016781

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No