HMB for Denutrition in Patients With Cirrhosis (HEPATIC)

NCT03285217 | Completed

• 1 other identifier: HEPATIC
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Cirrhosis is a late stage of hepatic fibrosis caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The World Health Organization (WHO) has reported that this condition accounts for 1.8% of all deaths in Europe (170,000 deaths/year). Patients with cirrhosis are characterized by severe metabolic alterations, which converge in a malnutritional state. Malnutrition encompasses glucose intolerance, chronic inflammation, altered gut microbiota, reduced muscle mass (sarcopenia), as well as loss and dysregulation of adipose tissue (adipopenia). Malnutrition is the most frequent complication that adversely affects the outcomes of cirrhotic patients. Yet, despite its clinical repercussions and potential reversibility, there are no effective therapies because our limited understanding of the mechanisms underlying this altered metabolism. β-hydroxy β-methylbutyrate (HMB) is a naturally produced substance regarded as safe and effective in preventing muscle loss during chronic diseases. Previous studies have indicated some beneficial effects of HMB itself or its parent metabolite, leucine, on adipose tissue, glucose intolerance, inflammation, and gut microbiota. This study aims to translate those beneficial effects to cirrhotic patients. The investigators hypothesize that HMB can improve cirrhosis-related metabolic abnormalities through its pleiotropic effects. The goals of this study are: i) to perform a randomized clinical trial to evaluate the efficacy of HMB, administered as nutritional supplementation, on clinical symptoms of cirrhosis. ii) to uncover the precise metabolic pathways that underlie HMB action, with a special focus on muscle, adipose tissue, and gut microbiota.

Conditions

Sarcopenia; Cirrhosis; Malnutrition

Keywords

HMB

Outcome Measures

Primary Outcomes (3)

• Changes in body composition

  changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA)

  Baseline, 6 wk, and final (12 wk)

• Liver Status I

  Child-Pugh Score

  Baseline, 6 wk, and final (12 wk)

• Liver Status II

  Liver transaminase enzymes: gamma glutamyl transpeptidase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT) will be combined in a liver functionality score

  Baseline, 6 wk, and final (12 wk)

Secondary Outcomes (4)

• Nutritional Status I

  Baseline, 6 wk, and final (12 wk)

• Nutritional Status II

  Baseline, 6 wk, and final (12 wk)

• Nutritional Status III

  Baseline, 6 wk, and final (12 wk)

• Inflammation

  Baseline, 6 wk, and final (12 wk)

Study Arms (2)

HMB

EXPERIMENTAL

HMB Group (n=30) will receive received twice a day for 3 months a specialized, nutrient-dense ready-to-drink liquid (Abbott Nutrition) with 350 kcal, 20 g protein, 11 g fat, 44 g carbohydrate, 1.5 g calcium-HMB, 160 IU vitamin D and other essential micronutrients.

Dietary Supplement: Ensure Plus Advance

Control

ACTIVE COMPARATOR

Control Group (n=30) will receive twice a day for 3 months another supplement with similar composition in macro- and micro-nutrients but without HMB

Dietary Supplement: Ensure High Protein

Interventions

Ensure Plus Advance DIETARY_SUPPLEMENT

Supplements, labeled only with the name of the participant and his/her identification number, will be provided to the participants in the Translational Research Unit of the Miguel Servet Hospital. Every 2 weeks, changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA). Likewise they will be asked about compliance and their diets will be controlled by a nutritionist. Fresh stool samples, urine and blood will be collected pre- and post treatment. An extensive bloodwork will be performed at the Clinical Biochemistry Service at the Miguel Servet Hospital (plasma HMB, total cholesterol, triglycerides, LDL\&HDL-cholesterol, free fatty acids, glucose, insulin, β-hydroxybutyrate, hs-CRP, and liver transaminases (AST, ALT, GGT).

HMB

Ensure High Protein DIETARY_SUPPLEMENT

Supplements, labeled only with the name of the participant and his/her identification number, will be provided to the participants in the Translational Research Unit of the Miguel Servet Hospital. Every 2 weeks, changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA). Likewise they will be asked about compliance and their diets will be controlled by a nutritionist. Fresh stool samples, urine and blood will be collected pre- and post treatment. An extensive bloodwork will be performed at the Clinical Biochemistry Service at the Miguel Servet Hospital (plasma HMB, total cholesterol, triglycerides, LDL\&HDL-cholesterol, free fatty acids, glucose, insulin, β-hydroxybutyrate, hs-CRP, and liver transaminases (AST, ALT, GGT).

Control

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• negative for hepatitis C virus (HCV)\&hepatitis B virus (HBV) , or alcohol-caused cirrhosis in stable clinical condition,
• alcoholic patients must have been abstinent for at least 6 months and be in Child's score of ≤7,
• no gastrointestinal bleeding for at least 3 months,
• no clinical, microbiological, or laboratory evidence of infection, renal failure, encephalopathy, malignancy, diabetes mellitus, comorbidities including heart failure or pulmonary disease,
• No use of medications that affect protein turnover, including corticosteroids and β-blockers.

Sponsors & Collaborators

• Instituto Aragones de Ciencias de la Salud: lead
• Refbio2: Trans-Pyrenean cooperation network for biomedical research: collaborator

Study Sites (1)

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (15)

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  PMID: 2646365 BACKGROUND

• Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, Sawyer MB. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol. 2012 Feb;10(2):166-73, 173.e1. doi: 10.1016/j.cgh.2011.08.028. Epub 2011 Sep 3.

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• Qiu J, Thapaliya S, Runkana A, Yang Y, Tsien C, Mohan ML, Narayanan A, Eghtesad B, Mozdziak PE, McDonald C, Stark GR, Welle S, Naga Prasad SV, Dasarathy S. Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-kappaB-mediated mechanism. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18162-7. doi: 10.1073/pnas.1317049110. Epub 2013 Oct 21.

  PMID: 24145431 BACKGROUND

• Floreani A, Variola A, Niro G, Premoli A, Baldo V, Gambino R, Musso G, Cassader M, Bo S, Ferrara F, Caroli D, Rizzotto ER, Durazzo M. Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis. Am J Gastroenterol. 2008 Aug;103(8):1959-65. doi: 10.1111/j.1572-0241.2008.01888.x. Epub 2008 Jun 28.

  PMID: 18564121 BACKGROUND

• Tilg H, Kaser A, Moschen AR. How to modulate inflammatory cytokines in liver diseases. Liver Int. 2006 Nov;26(9):1029-39. doi: 10.1111/j.1478-3231.2006.01339.x.

  PMID: 17032402 BACKGROUND

• Lin SY, Sheu WH, Chen WY, Lee FY, Huang CJ. Stimulated resistin expression in white adipose of rats with bile duct ligation-induced liver cirrhosis: relationship to cirrhotic hyperinsulinemia and increased tumor necrosis factor-alpha. Mol Cell Endocrinol. 2005 Mar 31;232(1-2):1-8. doi: 10.1016/j.mce.2005.01.006.

  PMID: 15737463 BACKGROUND

• Betrapally NS, Gillevet PM, Bajaj JS. Gut microbiome and liver disease. Transl Res. 2017 Jan;179:49-59. doi: 10.1016/j.trsl.2016.07.005. Epub 2016 Jul 15.

  PMID: 27477080 BACKGROUND

• Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J; DGEM (German Society for Nutritional Medicine); Ferenci P, Holm E, Vom Dahl S, Muller MJ, Nolte W; ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN Guidelines on Enteral Nutrition: Liver disease. Clin Nutr. 2006 Apr;25(2):285-94. doi: 10.1016/j.clnu.2006.01.018. Epub 2006 May 16.

  PMID: 16707194 BACKGROUND

• Plauth M, Cabre E, Campillo B, Kondrup J, Marchesini G, Schutz T, Shenkin A, Wendon J; ESPEN. ESPEN Guidelines on Parenteral Nutrition: hepatology. Clin Nutr. 2009 Aug;28(4):436-44. doi: 10.1016/j.clnu.2009.04.019. Epub 2009 Jun 11.

  PMID: 19520466 BACKGROUND

• Ney M, Vandermeer B, van Zanten SJ, Ma MM, Gramlich L, Tandon P. Meta-analysis: oral or enteral nutritional supplementation in cirrhosis. Aliment Pharmacol Ther. 2013 Apr;37(7):672-9. doi: 10.1111/apt.12252. Epub 2013 Feb 20.

  PMID: 23421379 BACKGROUND

• Koretz RL, Avenell A, Lipman TO. Nutritional support for liver disease. Cochrane Database Syst Rev. 2012 May 16;2012(5):CD008344. doi: 10.1002/14651858.CD008344.pub2.

  PMID: 22592729 BACKGROUND

• Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016 Dec;65(6):1232-1244. doi: 10.1016/j.jhep.2016.07.040. Epub 2016 Aug 8.

  PMID: 27515775 BACKGROUND

• Nguyen DL, Morgan T. Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view. Hepatol Int. 2014 Sep 1;8(2):447-51. doi: 10.1007/s12072-013-9497-1.

  PMID: 25525477 BACKGROUND

• Gluud LL, Dam G, Les I, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017 May 18;5(5):CD001939. doi: 10.1002/14651858.CD001939.pub4.

  PMID: 28518283 BACKGROUND

• Krebs HA, Lund P. Aspects of the regulation of the metabolism of branched-chain amino acids. Adv Enzyme Regul. 1976;15:375-94. doi: 10.1016/0065-2571(77)90026-7. No abstract available.

  PMID: 19935 BACKGROUND

MeSH Terms

Conditions

Sarcopenia; Fibrosis; Malnutrition

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pathologic Processes; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Alejandro Sanz-Paris, MD

  Hospital Miguel Servet

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 15, 2017
• Study Start: October 15, 2017
• Primary Completion: March 31, 2018
• Study Completion: December 31, 2019
• Last Updated: May 4, 2021

Record last verified: 2021-05

Locations

ES (1)