Fecal Microbiota Transplantation in Decompensated Cirrhosis

• ClinicalTrials.gov Identifier: NCT04842539
• Recruitment Status: Completed
• First Posted: April 13, 2021
• Last Update Posted: April 13, 2021
• Sponsor: Postgraduate Institute of Medical Education and Research
• Information provided by (Responsible Party): Radha K Dhiman, Postgraduate Institute of Medical Education and Research

Study Description

Brief Summary:

Cirrhosis of the liver is the culmination point of long-standing chronic liver disease hallmarked by the cardinal features of liver fibrosis and portal hypertension. The prognosis of patients with cirrhosis is punctuated by the onset of complications which denote the stage of decompensation characterized by ascites, hepatic encephalopathy (HE), and variceal bleeding.

Patients with cirrhosis have been demonstrated to have significant changes in their gut microbiota characterized by alteration in the intestinal microbiome (gut dysbiosis) as well as small intestinal bacterial overgrowth (SIBO). Gut dysbiosis has been closely linked to the complications associated with decompensated cirrhosis. Several studies have documented the alteration of gut microbiota in patients with hepatic encephalopathy.

Therapeutic modalities that restore normal gut flora and stabilize the gut liver axis are being extensively studied in the management of cirrhosis and its complications. Antibiotics, probiotics, and long-chain fatty acid supplementation are being evaluated as methods to restore the gut dysbiosis and consequently limit progressive liver damage.

Fecal Microbiota Transplantation (FMT) involves the infusion of intestinal microorganisms by the transfer of stool from a healthy individual into a diseased individual for restoration of normal intestinal flora.The ultimate goal of FMT is to replace aberrant native microbiota with a stable community of donor microorganisms. The treatment is based on the premise that an imbalance in the community of microorganisms residing in the gastrointestinal tract (i.e., dysbiosis) is associated with specific disease states. FMT has been well-established as a treatment modality to stably modify the gut microbiome and has been shown to be safe and efficacious in several disease states resulting from gut dysbiosis.

With this background, a trial is proposed to determine whether an FMT from a healthy donor to a patient with advanced cirrhosis improves overall survival and prognosis.

Condition or disease	Intervention/treatment	Phase
Liver Cirrhosis	Other: Fecal Microbiota Transplantation; Other: Standard of care	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Session of Fecal Microbiota Transplantation in Decompensated Cirrhosis: An Open-label Randomized Control Trial
• Actual Study Start Date: August 1, 2018
• Actual Primary Completion Date: November 30, 2019
• Actual Study Completion Date: November 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: FMT Arm; FMT Arm:30 grams stool homogenized with 100 mL normal saline and filtered administered a single time via nasojejunal tube.	Other: Fecal Microbiota Transplantation; In the Fecal Microbiota Transplantation procedure 100 ml volume of strained and filtered stool will be delivered through a nasojejunal tube.The recipient patient will be kept nil per oral for at least 4 hours prior to the stool instillation. 100 mL of freshly prepared stool suspension will be given.
Standard of care (SOC) Arm; Standard of care treatment with nutritional supplementation and other supportive care	Other: Standard of care; Nutritional supplementation and other supportive measures as per standard guidelines

Outcome Measures

Primary Outcome Measures :

1. Survival [ Time Frame: 180 day ]
   180 days

Secondary Outcome Measures :

1. Change in Child Turcotte Pugh Score [ Time Frame: 180 days ]
2. Change in MELD score [ Time Frame: 180 days ]
3. Change in MELD Na score [ Time Frame: 180 days ]
4. Change in ammonia level [ Time Frame: 28 days ]
5. Change in Interleukin level [ Time Frame: 28 days ]
6. Number of patients with incident Hepatic encephalopathy [ Time Frame: 180 days ]
7. Number of patients with incident Variceal Bleed [ Time Frame: 180 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Age 18-65 years Decompensated cirrhosis (of any etiology) based on clinical, radiological, or histological criteria Model for end-stage liver disease (MELD scores) between 12-21 were included.

Exclusion Criteria:

Ongoing bacterial infection requiring antibiotics Antibiotics/pre-pro biotics within the last 14 days, t Significant alcohol intake in the previous two months, Recent (<14 days) history of spontaneous bacterial peritonitis, HE or variceal bleed, History of substance abuse or psychiatric illness, HIV infection, Pregnant patients, Hepatocellular carcinoma or other known malignancy, t Prior liver transplantation or bariatric surgery, Immunosuppression, Inflammatory bowel disease Celiac disease, History of allergy to food substances

Contacts and Locations

Locations

India

Post Graduate Institute of Medical Education and Research

Chandigarh, India, 160012

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

  Study Documents (Full-Text)

Documents provided by Radha K Dhiman, Postgraduate Institute of Medical Education and Research:

Study Protocol and Statistical Analysis Plan  [PDF] August 1, 2018

More Information

• Responsible Party: Radha K Dhiman, Professor of Hepatology, Postgraduate Institute of Medical Education and Research
• ClinicalTrials.gov Identifier: NCT04842539
• Other Study ID Numbers: INT/IEC2018/2076
• First Posted: April 13, 2021
• Last Update Posted: April 13, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Radha K Dhiman, Postgraduate Institute of Medical Education and Research:

End-stage liver disease; Stool therapy; Microbiota; Related stool donor; Prognostic scores; Complications; Ammonia; Cytokines; Outcomes

Additional relevant MeSH terms:

Liver Cirrhosis; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases