HMB for Denutrition in Patients With Cirrhosis (HEPATIC)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 2
- 主要终点
- Changes in body composition
研究概览
简要总结
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.
详细描述
- Scientific & technical aspects
State of the art:
Patients with cirrhosis present a chronic inflammatory state and alterations in protein metabolism. These alterations lead to elevated levels of insulin and catecholamines along with the development of glucose intolerance and insulin resistance. The reduced availability of glucose as energy source translates into an accelerated starvation with reduced body fat mass (adipopenia) and loss of skeletal muscle mass (sarcopenia). This catabolic state reduces survival and post-liver transplant outcomes in patients with cirrhosis.
Loss of skeletal muscle mass or sarcopenia is the major component of malnutrition in cirrhosis and occurs in the majority of patients. Impaired ureagenesis and portosystemic shunting provoke skeletal muscle hyperammonemia which induces up-regulation of myostatin and increased autophagy, both of which contribute to sarcopenia.
The adipose tissue (AT) regulates energy homeostasis in the body regardless of the obesity status. Indeed, serum levels of the main adipose-produced cytokines (adipokines) such as leptin, adiponectin, and resistin have been found to be increased in cirrhotic patients as liver function worsens. Evidence demonstrated that adiponectin interacts with the immune/macrophage system and might be of relevance in many liver diseases. Likewise, hyperinsulinemia and increased tumor necrosis factor (TNF) α levels upregulated the adipose resistin gene in rat models of liver cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
HMB
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.
干预措施: Ensure Plus Advance (Dietary Supplement)
Control
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
干预措施: Ensure High Protein (Dietary Supplement)
结局指标
主要结局
Changes in body composition
时间窗: Baseline, 6 wk, and final (12 wk)
changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA)
Liver Status II
时间窗: Baseline, 6 wk, and final (12 wk)
Liver transaminase enzymes: gamma glutamyl transpeptidase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT) will be combined in a liver functionality score
Liver Status I
时间窗: Baseline, 6 wk, and final (12 wk)
Child-Pugh Score
次要结局
- Nutritional Status III(Baseline, 6 wk, and final (12 wk))
- Nutritional Status I(Baseline, 6 wk, and final (12 wk))
- Nutritional Status II(Baseline, 6 wk, and final (12 wk))
- Inflammation(Baseline, 6 wk, and final (12 wk))
研究者
Jose Miguel Arbones Mainar
Senior Researcher
Instituto Aragones de Ciencias de la Salud