A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced Serious Adverse Events up to Week 6
研究概览
简要总结
This research is studying the use of a new drug to learn about its safety and efficacy as a treatment for hepatic encephalopathy.
Eligible participants will be enrolled and given oral antibiotics followed by 14 days of the study drug (placebo vs.VE303). There will be visits as well as other procedures to collect blood and stool samples, and have tests of your cognition (thinking) for this research study.
The hypothesis is that VE303 will safely and effectively improve cognitive function in patients with a history of overt hepatic encephalopathy.
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
- Double (Participant, Investigator)
盲法说明
Study staff will remain blinded to subject randomization until the study period is over.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation
- •History of at least one episode of overt HE any time in the past
- •Prescribed both lactulose and rifaximin, and compliant with this treatment
排除标准
- •Current episode of overt HE
- •Variceal bleeding in the last 4 weeks
- •Gut-absorbable or intravenous antibiotic therapy in the last 28 days
- •Fecal microbiota transplant in the last 6 months
- •Use of probiotics in the last 2 weeks
- •Alcohol or illicit drug intake in the last 4 weeks
- •Primary sclerosing cholangitis as etiology of liver disease
- •History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis
- •Prior diagnosis of dementia or other primary neurocognitive disorder
- •Known hypersensitivity/allergy/intolerance to Vancomycin and any ingredients of VE303: sucrose, histidine, yeast extract, cysteine, metabisulfite, and microcrystalline cellulose
- •History of Roux-en-Y Gastric bypass
- •Any gastrointestinal surgery in the last year
- •Substantial immune compromise/deficiency (e.g., uncontrolled human immunodeficiency virus, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia)
- •Pregnancy or breast feeding
- •Model for end-stage liver disease (MELD) > 20
- •History of spontaneous bacterial peritonitis
- •Hemodialysis in the last 28 days
- •Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt in the last 3 months (permissible if placed >3 months before enrollment)
- •Unstable doses of opiates, benzodiazepines or other sedating medication
- •Chronic methadone or low dose benzodiazepines (for example) is acceptable
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Placebo
干预措施: oral vancomycin (Drug)
VE303
VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.
干预措施: VE303 (Drug)
VE303
VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.
干预措施: oral vancomycin (Drug)
结局指标
主要结局
Number of Participants Who Experienced Serious Adverse Events up to Week 6
时间窗: Week 6
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to Week 6
时间窗: baseline (pre-vancomycin), Week 6
This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18, where +6 is the best function and -18 is worst function.
次要结局
- Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26(26 weeks)
- Adverse Events up to Week 26(up to week 26)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26(baseline (pre-vancomycin), week 26)
- Time to Overt HE(up to 26 weeks)
- Change in Microbiome Composition From Pre-vancomycin to Week 26(baseline (pre-vancomycin), week 26)
- PHES From Pre-vancomycin to Week 26(pre-vancomycin up to week 26)
研究者
Patricia Bloom
Clinical Lecturer in Internal Medicine
University of Michigan