Safety and Tolerability of Fecal Microbiota Transplantation in Cirrhosis and Hepatic Encephalopathy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Safety and tolerability
研究概览
简要总结
Randomized, open-label safety, tolerability study with exploratory endpoints and pathophysiological evaluation of the FMT
Two groups of outpatients with cirrhosis will be randomized using random sequence generator into no-treatment and FMT groups.
详细描述
Group 1 (FMT group) will undergo the following procedures
Pre-FMT preparation:
We will obtain written informed consent per the IRB guidelines. After the patients are consented and are eligible, we will perform a detailed medical history and physical exam at day 0. We will also perform cognitive testing. As in prior studies, we will prescribe patients an antibiotic regimen. Drawing from ecological principles of microbial niche environments and data from recurrent Clostridium difficile infection, pre-treatment antibiotics are likely to increase the probability of disrupting the hosts intrinsic microbiota and creating an opportunity for a 'healthy' microbiota from the FMT to engraft.
After antibiotics and on the day of FMT:
At day 5, we will re-evaluate patients with a directed interval history and focused physical exam as needed. After ensuring that they are still candidates according to the inclusion/exclusion criteria, we will collect stool, urine and blood again for pre-FMT evaluation and urine for pregnancy tests from eligible women. Cognitive testing will be performed again.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cirrhosis diagnosed by either of the following in a patient with chronic liver disease
- •Liver Biopsy
- •Radiologic evidence of varices, cirrhosis or portal hypertension
- •Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1
- •Endoscopic evidence of varices or portal gastropathy
- •At least two episodes of hepatic encephalopathy, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
- •Age between 21 and 75
- •Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting)
排除标准
- •MELD score >17
- •WBC count <1000 cells/mm3
- •Platelet count<50,000/mm3
- •On the liver transplant list
- •TIPS in place
- •No HE episode within a month prior to the study
- •Patients allergic to ciprofloxacin, penicillins or metronidazole
- •Currently on absorbable antibiotics
- •Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed)
- •Hospitalization for any non-elective cause within the last 3 months
- •Patients who are aged >75 years
- •Patients who are pregnant or nursing (will be checked using a urine pregnancy test)
- •Patients who are incarcerated
- •Patients who are incapable of giving their own informed consent
- •Patients who are immuno-compromised due to the following reasons:
- •HIV infection (any CD4 count)
- •Inherited/primary immune disorders
- •Current or recent (<3 mos) treatment with anti-neoplastic agent
- •Current or recent (<3 mos) treatment with any immunosuppressant medications [including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil]. Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
- •Patients with a history of severe (anaphylactic) food allergy
- •Patients who have previously undergone FMT
- •Patients on renal replacement therapy
- •Patients who are unwilling or unable to hold the enemas
- •Patients with untreated, in-situ colorectal cancer
- •Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis) , eosinophilic gastroenteritis, celiac disease or irritable bowel syndrome
- •Major gastro-intestinal or intra-abdominal surgery in the last three months
- •Unable to comply with protocol requirements
- •Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
- •Patients with acute illness or fever on the day of planned FMT will be excluded with the option of including that subject at a future date
- •Any conditions for which, in opinion of MD, the treatment may pose a health risk
- •C. difficile in the stool at baseline (qPCR)
- •Grade 2-4 or complicated hemorrhoids
研究组 & 干预措施
FMT
Fecal transplant via enema once
干预措施: Fecal transplant (Biological)
No treatment
No transplant performed
结局指标
主要结局
Safety and tolerability
时间窗: 5 months
Defined by the rate of development of FMT-related SAE and withdrawal from the study in cirrhotic subjects
次要结局
- Microbiota composition and function(15 days)
- Cognitive functioning(15 days)
研究者
Jasmohan Bajaj
MD
Hunter Holmes Mcguire Veteran Affairs Medical Center