Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

益生菌酸奶治疗轻微肝性脑病

• 批准号: 7928052
• 负责人: Jasmohan S Bajaj
• 金额: $ 28.59万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928052
• 关键词: Address; Adherence; Adverse effects; Affect; Alcoholic Liver Cirrhosis; Alternative Medicine; Alternative Therapies; Area; Attention; Automobile Driving; Biological Markers; Blood; Cirrhosis; Clinical Trials; Cognitive; Complementary and alternative medicine; Complication; Consensus; DNA Sequence; Development; Diarrhea; Diet; Double-Blind Method; Encephalopathies; Evaluation; Feces; Food; Funding; Goals; Guidelines; Hepatic Encephalopathy; Impaired cognition; Intestines; Lactobacillus; Lactulose; Liver diseases; Metabolic; Morbidity - disease rate; Motor Vehicles; NMR Spectroscopy; National Center for Complementary and Alternative Medicine; Nutritional; Outcome; Participant; Patients; Performance; Pharmaceutical Preparations; Phase; Placebos; Polymerase Chain Reaction; Prevalence; Prevention; Probiotics; Proteins; Psychometrics; Quality of life; Randomized; Randomized Controlled Trials; Research; Research Personnel; Research Priority; Risk; Safety; Testing; Therapeutic; Traffic accidents; United States National Institutes of Health; Urine; Work; Yogurt; alternative treatment; base; comparison group; compliance behavior; cytokine; dietary supplements; group intervention; improved; interest; mortality; non-alcoholic; outcome forecast; primary outcome; prospective; randomized placebo controlled trial; randomized trial; rifaximin

DESCRIPTION (provided by applicant): Development of complementary and alternative medicine approaches to liver disease is a priority area at NCCAM. Minimal hepatic encephalopathy (MHE) is a significant complication of cirrhosis which can result in poor quality of life, impaired cognition and difficulty in driving motor vehicles with a high traffic accident risk. MHE is estimated to affect one half of the 5.5 million cirrhotics in the U.S. Despite these negative outcomes, there is no consensus on treatment of MHE. Currently available therapies for MHE act on intestinal flora but are limited by adverse effects (i.e. lactulose-induced diarrhea), which negatively impact adherence. Probiotic bacterial supplements, which also act on intestinal flora, are an emerging therapy for MHE. Our group has performed a pilot, randomized trial which demonstrated a significantly higher rate of MHE reversal with excellent adherence in patients randomized to probiotic yogurt compared to no therapy. This proposal intends to define Lactobacillus GG (LGG) as a biologically-based alternative therapy for MHE with special focus on metabolic and stool bacteriologic changes. The hypothesis of this Phase I proposal is: LGG will be safe and efficacious for the treatment of minimal hepatic encephalopathy compared to placebo in a randomized, double-blind trial. This will be carried out with four specific aims. Specific aim 1: To define the safety and tolerability of LGG in patients with minimal hepatic encephalopathy against placebo in a Phase I randomized controlled trial. Specific aim 2: To define the effect of LGG on intestinal microflora composition in cirrhotics with minimal hepatic encephalopathy using 16s stool DNA sequencing in a randomized, placebo-controlled trial. Specific aim 3: To determine the effect of LGG on metabolic biomarkers and cytokines in stool, urine and blood using nuclear magnetic resonance spectroscopy in minimal hepatic encephalopathy. Specific aim 4: To determine the effect of LGG on psychometric function in patients with minimal hepatic encephalopathy. The specific aim and sub-aims will be tested in 40 patients with non-alcoholic cirrhosis and MHE: 20 randomized to LGG and 20 randomized to placebo to be taken BID for 8 weeks with detailed psychometric, metabolic, anthropometric and bacteriologic evaluation. Results generated from this study will form the basis for a RO1 proposal to develop the use of probiotics as a biologically-based alternative treatment with long-term outcomes of prognosis, development of overt encephalopathy and prevention of traffic accidents in patients with MHE.

描述（由申请人提供）：开发肝病的补充和替代医学方法是NCCAM的优先领域。最小的肝脑病（MHE）是肝硬化的重要并发症，可能导致生活质量差，认知受损和驾驶具有高交通事故风险的机动车的困难。据估计，MHE在美国的550万个肝硬化药物中，尽管有这些负面结果，但对MHE的治疗仍未达成共识。目前针对肠道菌群的MHE法案可用的疗法，但受到不良影响（即乳糖诱导的腹泻）的限制，这会对依从性产生负面影响。益生菌的细菌补充剂也对肠菌群作用，是MHE的新兴疗法。我们的小组进行了一项试验，随机试验，与无治疗相比，在随机分配至益生菌酸奶的患者中，MHE逆转的率明显更高，并且依从性较高。该建议旨在将乳酸乳杆菌（LGG）定义为基于生物学上的MHE替代疗法，以特别关注代谢和粪便杆菌的变化。 该阶段I提案的假设是：与安慰剂相比，在随机的双盲试验中，LGG对于最小的肝脑病治疗将是安全有效的。 这将以四个特定目标进行。 具体目的1：在I期随机对照试验中，定义LGG对安慰剂的最小肝脑病患者的安全性和耐受性。 具体目的2：在一项随机的，安慰剂对照的试验中，使用16S粪便DNA测序来定义LGG对肝脏毛状肠菌组成的影响。 具体目标3：确定LGG对最小肝性脑病中的核磁共振光谱法对粪便，尿液和血液中代谢生物标志物和细胞因子的影响。 具体目标4：确定LGG对最小肝脑病患者心理测量功能的影响。 特定的目标和子摄入量将在40例非酒精性肝硬化和MHE的患者中进行测试：20随机分配到LGG，20个随机分配给安慰剂，以竞标8周，并进行详细的心理测定，代谢，人体测定和细菌学评估。这项研究产生的结果将构成RO1提案的基础，以开发益生菌作为一种基于生物学的替代治疗，并具有长期预后的结果，明显的脑病的发展以及预防MHE患者的交通事故。