Effect of Exercise With and Without HMB on Body Composition and Muscle Strength in Sickle Cell Anaemia

Effects of β-hydroxy-β-methyl Butyrate Supplementation and Resistance Exercise on Body Composition, Muscle Strength and Protein Oxidation in Sickle Cell Anaemia.

Wasting is a common and significant problem in sickle cell anaemia (SCA) that correlates with poorer clinical outcome such as frequent painful crises, acute chest syndrome and sub normal resistance to infection. Thus, improvement of nutritional status in SCA holds the potential of ameliorating the course of the disease. Elevated haemolysis and its effects are associated with hypermetabolism and have resulted in higher rates of protein breakdown and synthesis, and energy expenditure. Offering more food has not optimized nutritional status and metabolic performance in free-living patients with SCA. Moreover, appetite might be suppressed. Supplementation with β-hydroxy-β-methylbutyrate (HMB), which is produced in the body from leucine, has been shown to have inhibitory effect on protein breakdown and to promote lean tissue synthesis in humans with sarcopenia. Also, HMB has been implicated as an ergogenic tool to promote exercise performance and skeletal muscle hypertrophy. Therefore, the investigators hypothesize that in individuals with SCA, an intervention of resistance exercise with HMB supplement will have a greater enhancing effect on muscle mass and strength compared to receiving resistance exercise without HMB.

Study Overview

• Status: Unknown
• Conditions: Sickle Cell Anemia
• Intervention / Treatment: Dietary supplement: placebo; Behavioral: Resistance exercise; Dietary supplement: β-hydroxy-β-methylbutyrate

Detailed Description

The investigators aim to measure muscle strength, body composition and whole body protein oxidation in two groups of adults with SCA within one week before and after 9 weeks of intervention in a randomized, double blinded study. One group (n =12 ) will receive an intervention of resistance exercise and HMB supplement, and the other group (n=12) will receive resistance exercise and a placebo (maltodextrin). Participants will be assigned a study code and all information and samples will be stored under the assigned code.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI < 18.5 kg/m2

Exclusion Criteria:

• BMI > 19 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: exercise combined with β-hydroxy-β-methylbutyrate (HMB); Resistance Exercise ( 3d/week) and HMB: 3g/d as three 1g capsules orally, for 9 weeks	Behavioral: Resistance exercise; effect of exercise and an anabolic agent on body composition, muscle strength, phenylalanine and protein oxidation.; Other Names: HMB; Dietary supplement: β-hydroxy-β-methylbutyrate
Placebo Comparator: exercise combined with placebo; Resistance exercise ( 3d/week) and placebo as 3g/d maltodextrin as three 1g capsules orally, for 9 weeks	Dietary supplement: placebo; Other Names: maltodextrin; Behavioral: Resistance exercise; effect of exercise and an anabolic agent on body composition, muscle strength, phenylalanine and protein oxidation.; Other Names: HMB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition assessment using deuterium dilution method	Change between baseline and after 3 months of intervention	3 months
Body composition assessment using Dual-energy X-ray absorptiometry	Change between baseline and after 3 months of intervention	3 months
Body composition assessment using bioelectrical impedance	Change between baseline and after 3 months of intervention	3 months
muscle strength assessment using the 1-repetition maximum method for the lower body (leg extension and or seated leg press) and upper body (bench press, bicep preacher curl)	Change between baseline and after 3 months of intervention	3 months
Protein oxidation using established stable isotope tracer method with oral doses of isotopically labelled sodium bicarbonate and phenylalanine	Change between baseline and after 3 months of intervention	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary intake using three 24 h dietary recall before and after intervention	Change between baseline and after 3 months of intervention	30 min
Resting metabolic rate using indirect calorimetry before and after intervention	Change between baseline and after 3 months of intervention	30 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with intervention-related abnormal laboratory values as assessed by blood haematology (anaemia profile,white blood cells count, platelet count)	Three measurements at baseline, mid point of intervention and at end of intervention	3 months
Number of participants with intervention-related abnormal laboratory values as assessed by blood chemistry (liver function and lipid profile)	Three measurements at baseline, mid point of intervention and at end of intervention	3 months
Number of participants with intervention-related adverse effect on emotional profile according to the Circumplex Test of emotion questionnaire	Assessment at baseline and at the end of each week during the intervention	weekly for 3 months
Number of participants with intervention-related adverse health effect as assessed by completing a health-related questionnaire	Assessment at baseline and at the end of each week during the intervention	weekly for 3 months

Collaborators and Investigators

• Sponsor: The University of The West Indies
• Investigators: Principal Investigator: Asha V Badaloo, PhD, Tropical Metabolism Research Unit, CAIHR, University of the West Indies; Study Director: Marvin E Reid, MBBS, PhD, Tropical Metabolism Research Unit, CAIHR, University of the West Indies

Publications and helpful links

General Publications

• Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review. Nutr Metab (Lond). 2008 Jan 3;5:1. doi: 10.1186/1743-7075-5-1.
• Badaloo A, Jackson AA, Jahoor F. Whole body protein turnover and resting metabolic rate in homozygous sickle cell disease. Clin Sci (Lond). 1989 Jul;77(1):93-7. doi: 10.1042/cs0770093.
• Jackson AA, Landman JP, Stevens MC, Serjeant GR. Urea kinetics in adults with homozygous sickle cell disease. Eur J Clin Nutr. 1988 Jun;42(6):491-6.
• Rathmacher JA, Nissen S, Panton L, Clark RH, Eubanks May P, Barber AE, D'Olimpio J, Abumrad NN. Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. JPEN J Parenter Enteral Nutr. 2004 Mar-Apr;28(2):65-75. doi: 10.1177/014860710402800265.
• Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC Jr, Connelly AS, Abumrad N. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985). 1996 Nov;81(5):2095-104. doi: 10.1152/jappl.1996.81.5.2095.
• Borack MS, Volpi E. Efficacy and Safety of Leucine Supplementation in the Elderly. J Nutr. 2016 Dec;146(12):2625S-2629S. doi: 10.3945/jn.116.230771. Epub 2016 Nov 9.
• Cruz-Jentoft AJ. Beta-Hydroxy-Beta-Methyl Butyrate (HMB): From Experimental Data to Clinical Evidence in Sarcopenia. Curr Protein Pept Sci. 2018;19(7):668-672. doi: 10.2174/1389203718666170529105026.
• Heyman MB, Vichinsky E, Katz R, Gaffield B, Hurst D, Castillo R, Chiu D, Kleman K, Ammann AJ, Thaler MM, et al. Growth retardation in sickle-cell disease treated by nutritional support. Lancet. 1985 Apr 20;1(8434):903-6. doi: 10.1016/s0140-6736(85)91677-0.
• Di Buono M, Wykes LJ, Ball RO, Pencharz PB. Dietary cysteine reduces the methionine requirement in men. Am J Clin Nutr. 2001 Dec;74(6):761-6. doi: 10.1093/ajcn/74.6.761.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2013
• Primary Completion (Actual): March 7, 2017
• Study Completion (Anticipated): November 15, 2019

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Anemia, Sickle Cell
• Other Study ID Numbers: HMB001

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