Independent and Combined Effects of Resistance Exercise Training and β-hydroxy β-methylbutyrate Plus Vitamin D

Independent and Combined Effects of Resistance Exercise Training and β-hydroxy β-methylbutyrate Plus Vitamin D on Body Composition and Skeletal Muscle Health

During middle-age, humans begin to lose muscle mass and strength. With increasing age the deterioration of muscle health is associated with a decline in quality of life and the loss of independence. β-hydroxy β-methylbutyrate (HMB) plus Vitamin D (VitD) have been proposed to increase skeletal muscle mass, contractile function and improve body composition but has yet to be evaluated in middle-aged women. The overall goal of this study is to determine the effects of HMB +VitD supplementation during 12 weeks of resistance exercise training or a non-exercise control on body composition, skeletal muscle size, and skeletal muscle function in middle-aged women.

Study Overview

• Status: Unknown
• Conditions: Aging; Skeletal Muscle
• Intervention / Treatment: Behavioral: Non-Exercise Control; Dietary supplement: Placebo; Dietary supplement: HMB+VitD; Behavioral: Resistance Exercise Training

Detailed Description

To determine if HMB+VitD supplementation is an effective strategy to help prevent the loss of skeletal muscle size, skeletal muscle function and body composition in middle-aged women, forty eight women (45-60 yrs old) will be recruited to complete a 12-week intervention (n=12 per group; 4 groups). Participants will be randomized to complete a non-exercise control period or a resistance exercise training program. In a double-blinded fashion, participants in the non-exercise or resistance exercise groups will be randomized to consume either placebo or HMB+VitD. Before and after each intervention the investigators will evaluate skeletal muscle size, skeletal muscle function, and body composition.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adam Konopka, PhD; Phone Number: 1 217 300 5844; Email: ark@illinois.edu
• Study Contact Backup: Name: Alexander Nichol, MS; Phone Number: 1 708 903 1720; Email: adnicho2@illinois.edu

Study Locations

• United States
  • Illinois
    • Urbana, Illinois, United States, 61822
      • Recruiting
      • Freer Hall
      • Contact: Adam Konopka; Phone Number: 217-300-5844; Email: ark@illinois.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women between 45 and 60 years old
• Women with a BMI < 35 kg/m2
• Sedentary (< 30 minutes of structured physical activity 3 times per week)
• Weight stable for 3 months prior (+/- 5kg)

Exclusion Criteria:

• Body mass index > 35 kg/m2
• Type 1 or Type 2 diabetes
• Uncontrolled hypertension
• Active cancer, cancer in remission, or having received treatment for any form of cancer in the previous 5 years
• Cardiovascular disease (e.g., peripheral artery disease and peripheral vascular disease)
• Uncontrolled thyroid function
• Chronic and/or regular consumption of medication known to influence skeletal muscle metabolism
• Use of Vitamin D (>2000 IU) or β-hydroxy β-methylbutyrate
• Tobacco use
• Any condition that limits exercise training (e.g., chronic obstructive pulmonary disease, neuromuscular disorder, moderate or severe cognitive impairment, Alzheimer's disease, vertigo, dizziness)
• High alcohol consumption defined as more than 8 drinks per week for women
• Unwilling to undergo any study-related procedures
• Pregnancy
• Abnormal liver or kidney enzymes determined in blood chemistry panel
• Bleeding/clotting disorders or blood thinning medications (e.g., warfarin, heparin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Non-exercise control with placebo; Participants will be asked to maintain their normal physical activity and dietary habits during the 12-week intervention. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 placebo capsules (calcium lactate), twice a day with a meal or snack for a total of 6 capsules per day. Placebo capsules match the size, color, weight, and number of capsules per dose compared to the β-hydroxy β-methylbutyrate (HMB) Plus Vitamin D (VitD) capsules.	Behavioral: Non-Exercise Control; Participants will not perform structured exercise and will continue with their normal physical activity for 12-weeks.; Dietary supplement: Placebo; Participants will be given placebo capsules to consume for 12-weeks.
EXPERIMENTAL: Non-exercise control with HMB+VitD; Participants will be asked to maintain their normal physical activity and dietary habits during the 12-week intervention. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 HMB+VitD capsules, twice a day with a meal or snack for a total of 6 capsules per day. Each capsule contains 500 mg calcium HMB and 333.33 IU Vitamin D for a total of 3.0 g HMB and 2000 IU Vitamin D per day.	Behavioral: Non-Exercise Control; Participants will not perform structured exercise and will continue with their normal physical activity for 12-weeks.; Dietary supplement: HMB+VitD; Participants will be given HMB+VitD capsules to consume for 12-weeks
ACTIVE_COMPARATOR: Resistance exercise training with placebo; Participants will complete 12-weeks (3 days per week) of a whole-body progressive resistance exercise training program. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 placebo capsules (calcium lactate), twice a day with a meal or snack for a total of 6 capsules per day. Participants will be asked to take capsules ~30-60 minutes before resistance exercise. Placebo capsules match the size, color, weight, and number of capsules per dose compared to the HMB + VitD capsules.	Dietary supplement: Placebo; Participants will be given placebo capsules to consume for 12-weeks.; Behavioral: Resistance Exercise Training; Participants will complete a 12-week whole-body progressive resistance exercise training program.
EXPERIMENTAL: Resistance exercise training with HMB+VitD; Participants will complete 12-weeks (3 days per week) of a whole-body progressive resistance exercise training program. Physical activity, diet, urine and blood samples will be collected every 4 weeks. Each participant will consume 3 HMB+VitD capsules, twice a day with a meal or snack for a total of 6 capsules per day. Participants will be asked to take capsules ~30-60 minutes before resistance exercise. Each capsule contains 500 mg calcium HMB and 333.33 IU Vitamin D for a total of 3.0 g HMB and 2000 IU Vitamin D per day.	Dietary supplement: HMB+VitD; Participants will be given HMB+VitD capsules to consume for 12-weeks; Behavioral: Resistance Exercise Training; Participants will complete a 12-week whole-body progressive resistance exercise training program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal Muscle Function - Knee extensor isometric performance	Knee extensor isometric performance will be assessed by a dynamometer. Muscle strength will also be determined by 1 repetition maximum for leg extension, leg curl and leg press exercises.	Change from baseline to after the 12 week intervention
Skeletal Muscle Function - Knee extensor isokinetic performance	Knee extensor isokinetic performance will be assessed by a dynamometer.	Change from baseline to after the 12 week intervention
Skeletal Muscle Function - Fatigue	Knee extensor fatigue will be assessed by a dynamometer.	Change from baseline to after the 12 week intervention
Skeletal Muscle Cross Sectional Area	Skeletal muscle cross sectional area will be assessed via magnetic resonance imaging (MRI).	Change from baseline to after the 12 week intervention
Skeletal Muscle Volume	Skeletal muscle volume will be assessed via magnetic resonance imaging (MRI).	Change from baseline to after the 12 week intervention
Body Composition - Mass	Fat and fat free mass will be measured using by a dual x-ray absorptiometry (DEXA) scan.	Change from baseline to after the 12 week intervention
Body Composition - Percentage	Fat and fat free percent will be measured using by a dual x-ray absorptiometry (DEXA) scan.	Change from baseline to after the 12 week intervention
Skeletal Muscle Mitochondrial Respiration	Mitochondrial respiration will be assessed using high-resolution respirometry in permeabilized muscle fibers.	Change from baseline to after the 12 week intervention
Skeletal Muscle Mitochondrial Hydrogen Peroxide Emissions	Mitochondrial hydrogen peroxide emissions will be assessed using high-resolution fluorometry in permeabilized muscle fibers.	Change from baseline to after the 12 week intervention
Myofiber Size	Cross sectional area of muscle fibers will be evaluated with immunohistochemistry.	Change from baseline to after the 12 week intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Density	Bone mineral density will be evaluated by a dual x-ray absorptiometry (DEXA) scan.	Change from baseline to after the 12 week intervention

Collaborators and Investigators

• Sponsor: University of Illinois at Urbana-Champaign
• Collaborators: Metabolic Technologies Inc.
• Investigators: Principal Investigator: Adam Konopka, PhD, University of Illinois at Urbana-Champaign

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: February 18, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (ACTUAL): February 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 093635

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: No
• Studies a U.S. FDA-regulated device product: No