Probiotic LGG in Patients With Minimal Hepatic Encephalopathy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- Safety of LGG
研究概览
简要总结
This research proposes to find whether the probiotic lactobacillus GG is safe and well tolerated in patients with minimal hepatic encephalopathy. We also want to get insight into the mechanisms of action of LGG.
详细描述
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.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18-65 years
- •Histological evidence of cirrhosis
- •Maintenance of cirrhosis treatment and stability for 6 months
- •Mini-mental state exam score > 25
- •Presence of MHE on psychometric testing
排除标准
- •Rx for MHE or OHE
- •Antibiotics within 6 weeks
- •Yogurt consumption within 2 weeks
- •Neutrophil count < 500
- •Inflammatory bowel disease
- •History of pancreatitis
- •Hepato-cellular carcinoma
- •Recent (6 weeks) gastrointestinal bleed
- •Recent (6 months) alcohol intake
- •Psychoactive medications (including interferon/antipsychotics)
- •Liver transplant
结局指标
主要结局
Safety of LGG
时间窗: 3 years
次要结局
- Bacteriology measured in the stool flora by specialized non-culture techniques(3 years)
- Quality of life measured by sickness impact profile(3 years)
- Metabonomics and psychometric testing using a standard psychometric battery(3 years)