Microbiota Transplant Therapy to Prevent HE Recurrence in a Phase 2B Multi-Center Trial of Veterans With Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 162
- 试验地点
- 3
- 主要终点
- Recurrence of Hepatic Encephalopathy (HE)
研究概览
简要总结
The goal of this clinical trial is to find out whether changing the microbes in the bowels of Veterans with cirrhosis and hepatic encephalopathy (a condition that affects the brain as a result of liver problems) using capsules made from microbes from healthy people can prevent future episodes of hepatic encephalopathy.
详细描述
Wartime injuries as well as metabolic disorders can result in liver injury directly or indirectly through PTSD, metabolic disorders, and/or alcohol misuse. These liver injuries culminate in cirrhosis, which affects 4.9 million patients in the US, >80,000 of whom are Veterans. Moreover, numerous Veterans with cirrhosis remain undiagnosed, suggesting these numbers are an underestimation. A major complication of cirrhosis, which is exacerbated by alcohol misuse and PTSD, is hepatic encephalopathy (HE), which affects >50% of Veterans with cirrhosis. Current HE therapies are lactulose (inexpensive but difficult to tolerate) and rifaximin (expensive and second line). However, despite these therapies, a large group of patients have recurrent HE episodes. These recurrences worsen clinical (readmissions, falls, death), psychosocial (cumulative brain injury, poor quality of life, disability, stress on the family), and financial outcomes to the patients, families, and the VHA. Microbiota transplant therapy (MTT) or fecal microbiota transplant (FMT) has the potential to interrupt this cycle. There are Phase 1 and Phase 2a randomized controlled trials (RCTs) published that defined safe and acceptable MTT routes for Veterans with HE. MTT was acceptable to most Veterans who were approached. However, the impact of MTT in preventing HE recurrence in a multi-center context is unclear, especially in those on lactulose only versus those on rifaximin.
The central hypothesis is: Microbial transplant therapy delivered through capsules will significantly reduce the rate of HE recurrence regardless of lactulose or rifaximin use compared to placebo in a multi-center double-blind, placebo-controlled, randomized clinical trial of Veterans with cirrhosis.
In a 6-month double-blind, multi-center, placebo-controlled, randomized clinical trial in Veterans with cirrhosis and HE on lactulose or rifaximin, these specific aims will be used to test this hypothesis:
Aim 1:Determine the rate of HE recurrence in MTT versus placebo-randomized groups: Patients from each site will be randomized 1:1 into receiving MTT or placebo capsules, which will be administered twice a day for 2 weeks. Patients will be followed monthly for 6 months. Recurrence of HE will be defined using standard criteria and will be the primary outcome. Stratification by lactulose use alone or lactulose and rifaximin will be performed.
Aim 2: Determine the effect of MTT on all-cause hospitalizations, death, and liver transplant compared to placebo. This analysis will study safety outcomes other than HE between the groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •21 years of age
- •Cirrhosis diagnosed by any 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 <110,000 or AST/ALT ratio>1
- •Endoscopic evidence of varices or portal hypertensive gastropathy
- •Prior overt HE (patient can be on lactulose and/or rifaximin 4 weeks stable dosing)
- •Able to give written, informed consent [mini-mental status exam (MMSE)]>25 at the time of consenting)
- •For lactulose only group: Prior HE not on rifaximin
排除标准
- •Disease-related:
- •MELD3.0 score>22
- •WBC count<1000
- •non-elective hospitalization or overt HE episode within 1 month
- •on dialysis
- •known untreated, luminal GI cancer
- •chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease, microscopic colitis, eosinophilic gastroenteritis or celiac disease)
- •Safety-related:
- •Current dysphagia
- •History of aspiration, intestinal obstruction or non-medication induced gastroparesis
- •Ongoing absorbable antibiotic use
- •History of anaphylactic food allergy
- •Allergy to ingredients in the capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
- •Adverse event attributable to prior FMT (7) ASA Class V
- •Pregnant or nursing patients
- •Acute illness or fever on the day of planned FMT
- •History of spontaneous bacterial peritonitis
研究组 & 干预措施
MTT
Microbiota transplant therapy (MTT) capsules
干预措施: Microbiota transplant therapy (MTT) capsules (Biological)
Placebo
Placebo capsule
干预措施: Placebo capsule (Other)
结局指标
主要结局
Recurrence of Hepatic Encephalopathy (HE)
时间窗: 6 months
HE episodes that requires hospitalization, ER visits, or medication changes prompted under medical supervision.
次要结局
- Liver transplant(6 months)
- Non-elective Hospitalizations(6 months)
- Health-related quality of life (HRQOL) assessment: Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)(6 months)
- Health-related quality of life (HRQOL) assessment: Sickness Impact Profile (SIP)(6 months)
- Cognitive testing: Psychometric Hepatic Encephalopathy score (PHES)(6 months)
- Cognitive testing: EncephalApp Stroop(6 months)
- Death(6 months)