Clinical trial NCT04001907: Effect of Exercise With and Without HMB on Body Composition and Muscle Strength in Sickle Cell Anaemia
Official title: Effects of β-hydroxy-β-methyl Butyrate Supplementation and Resistance Exercise on Body Composition, Muscle Strength and Protein Oxidation in Sickle Cell Anaemia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sickle Cell Anemia
Lead sponsor: The University of The West Indies
Sponsor class: OTHER
First posted: 2019-06-28
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* BMI \< 18.5 kg/m2

Exclusion Criteria:

* BMI \> 19 kg/m2

Primary outcomes:
measure: Body composition assessment using deuterium dilution method
timeFrame: 3 months
measure: Body composition assessment using Dual-energy X-ray absorptiometry
timeFrame: 3 months
measure: Body composition assessment using bioelectrical impedance
timeFrame: 3 months
measure: 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)
timeFrame: 3 months
measure: Protein oxidation using established stable isotope tracer method with oral doses of isotopically labelled sodium bicarbonate and phenylalanine
timeFrame: 3 months
Secondary outcomes:
measure: Dietary intake using three 24 h dietary recall before and after intervention
timeFrame: 30 min
measure: Resting metabolic rate using indirect calorimetry before and after intervention
timeFrame: 30 min
Other outcomes:
measure: Number of participants with intervention-related abnormal laboratory values as assessed by blood haematology (anaemia profile,white blood cells count, platelet count)
timeFrame: 3 months
measure: Number of participants with intervention-related abnormal laboratory values as assessed by blood chemistry (liver function and lipid profile)
timeFrame: 3 months
measure: Number of participants with intervention-related adverse effect on emotional profile according to the Circumplex Test of emotion questionnaire
timeFrame: weekly for 3 months
measure: Number of participants with intervention-related adverse health effect as assessed by completing a health-related questionnaire
timeFrame: weekly for 3 months
Locations:
Study officials:
affiliation: Tropical Metabolism Research Unit, CAIHR, University of the West Indies
name: Asha V Badaloo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tropical Metabolism Research Unit, CAIHR, University of the West Indies
name: Marvin E Reid, MBBS, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.