Clinical trial NCT03605147: The Effect of Calcium β-hydroxy-β-methylbutyrate (CaHMB) Supplementation in Sarcopenia in Liver Cirrhosis
Official title: The Effect of Calcium β-hydroxy-β-methylbutyrate Supplementation in Sarcopenia in Liver Cirrhosis：A Randomized Double-blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sarcopenia
Cirrhosis, Liver
Keywords: HMB
sarcopenia
liver cirrhosis
chronic liver disease
malnutrition
muscle wasting
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2018-07-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the effect of CaHMB in the treatment of sarcopenia in liver cirrhosis.

Detailed description: The study is a randomized double-blind controlled trial. Patients randomly enter into two treatment groups: 1) the CaHMB group and 2) the placebo group. Treatment allocation is by block randomization, with an one-to-one ratio for CaHMB and placebo. The results are concealed in opaque envelopes. Patients will report their daily diets with an online software. Patients will come for clinic after 4 weeks and 12 weeks, receiving laboratory tests and sarcopenia evaluation, and events of primary and secondary outcomes will be analyzed.

Eligibility criteria: Inclusion Criteria:

1. diagnosed of cirrhosis with imaging or liver biopsy;
2. diagnosis of portal hypertension with endoscopy or radiography；
3. assessed total muscle mass at the level of L3 (\<42 cm2/m2 for male and \<38 cm2/m2 for female)
4. has signed an informed consent form.

Exclusion Criteria:

1. diagnosed as hepatic cell cancer;
2. complicated with malignancy, renal failure, diabetes mellitus;
3. comorbidities including heart failure or pulmonary disease;
4. current use of drugs that affect skeletal muscle metabolism;
5. be allergic to the experimental food;
6. participated other clinical trials in the past 3 months;
7. other conditions that researchers consider not suitable for this study

Primary outcomes:
measure: Changes in skeletal muscle mass
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Changes in total body weight
timeFrame: Baseline and 12 weeks
measure: Grip strength
timeFrame: Baseline and 12 weeks
measure: Protein metabolic markers
timeFrame: Baseline and 12 weeks
measure: Changes in intramuscular fat deposition
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Shiyao Chen, doctor
role: STUDY_CHAIR
References:
citation: Chan HL, Jia J. Chronic hepatitis B in Asia-new insights from the past decade. J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:131-7. doi: 10.1111/j.1440-1746.2010.06544.x.
citation: Holecek M. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):529-541. doi: 10.1002/jcsm.12208. Epub 2017 May 10.
citation: Sinclair M, Gow PJ, Grossmann M, Angus PW. Review article: sarcopenia in cirrhosis--aetiology, implications and potential therapeutic interventions. Aliment Pharmacol Ther. 2016 Apr;43(7):765-77. doi: 10.1111/apt.13549. Epub 2016 Feb 5.
citation: Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998 Apr 15;147(8):755-63. doi: 10.1093/oxfordjournals.aje.a009520.
citation: Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010 Jul;39(4):412-23. doi: 10.1093/ageing/afq034. Epub 2010 Apr 13.
citation: Tsien C, Davuluri G, Singh D, Allawy A, Ten Have GA, Thapaliya S, Schulze JM, Barnes D, McCullough AJ, Engelen MP, Deutz NE, Dasarathy S. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology. 2015 Jun;61(6):2018-29. doi: 10.1002/hep.27717. Epub 2015 Feb 27.
citation: Wilkinson DJ, Hossain T, Limb MC, Phillips BE, Lund J, Williams JP, Brook MS, Cegielski J, Philp A, Ashcroft S, Rathmacher JA, Szewczyk NJ, Smith K, Atherton PJ. Impact of the calcium form of beta-hydroxy-beta-methylbutyrate upon human skeletal muscle protein metabolism. Clin Nutr. 2018 Dec;37(6 Pt A):2068-2075. doi: 10.1016/j.clnu.2017.09.024. Epub 2017 Oct 6.
citation: Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. 2012 Mar;27(3):430-41. doi: 10.1111/j.1440-1746.2011.06951.x.
citation: Takaguchi K, Moriwaki H, Doyama H, Iida M, Yagura M, Shimada N, Kang M, Yamada H, Kumada H. Effects of branched-chain amino acid granules on serum albumin level and prognosis are dependent on treatment adherence in patients with liver cirrhosis. Hepatol Res. 2013 May;43(5):459-66. doi: 10.1111/j.1872-034X.2012.01097.x. Epub 2012 Oct 10.
citation: Plank LD, Gane EJ, Peng S, Muthu C, Mathur S, Gillanders L, McIlroy K, Donaghy AJ, McCall JL. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology. 2008 Aug;48(2):557-66. doi: 10.1002/hep.22367.
citation: Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016 Sep;46(10):951-63. doi: 10.1111/hepr.12774.