Fecal Microbiota Transplantation in Decompensated Cirrhosis

Single Session of Fecal Microbiota Transplantation in Decompensated Cirrhosis: An Open-label Randomized Control Trial

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.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Other: Fecal Microbiota Transplantation; Other: Standard of care

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	180 days	180 day

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Child Turcotte Pugh Score	180 days
Change in MELD score	180 days
Change in MELD Na score	180 days
Change in ammonia level	28 days
Change in Interleukin level	28 days
Number of patients with incident Hepatic encephalopathy	180 days
Number of patients with incident Variceal Bleed	180 days

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: April 3, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Microbiota; Outcomes; Complications; Cytokines; End-stage liver disease; Stool therapy; Related stool donor; Prognostic scores; Ammonia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: INT/IEC2018/2076

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No