A Prospective, Randomized, Placebo-Controlled Pilot Study to Characterize the Intestinal Microbiome and to Evaluate the Safety and Fecal Microbiome Changes Following Administration of Lyophilized PRIM-DJ2727 or Placebo Given Orally in Subjects With Nonalcoholic Fatty Liver Disease

A Prospective, Randomized, Placebo-Controlled Pilot Study to Characterize the Intestinal Microbiome and to Evaluate the Safety and Fecal Microbiome Changes Following Twice Weekly Administration of Lyophilized PRIM-DJ2727 or Placebo Given Orally for 12 Weeks in Subjects With Nonalcoholic Fatty Liver Disease (NAFLD)

Potential subjects with non-alcoholic fatty liver disease (NAFLD) will be identified by gastroenterologists (study investigators). Twelve eligible subjects with NAFLD will be randomly assigned to receive either active fecal microbiota transplantation in orally administered capsules or Placebo capsules and dosed twice weekly for 12 weeks. .

Study Overview

• Status: Not yet recruiting
• Conditions: Nonalcoholic Fatty Liver Disease (NAFLD) With History of Diabetes Melitus
• Intervention / Treatment: Drug: PRIM-DJ2727; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 18 years of age
2. For sexually active male and female subjects of childbearing potential, agree to use an effective method of birth control during the study.
3. For female subjects of childbearing potential, a negative urine Qualitative HCG pregnancy test at enrollment and on the Week 1, Day 1 of the Treatment prior to administration of study drug.
4. Willing and able to sign an informed consent form and attend study assessments and follow up visits.
5. A documented diagnosis of NAFLD without cirrhosis based on imaging or clinical judgment of a gastroenterologist or hepatologist.
6. History of diabetes mellitus
7. Has an attending physician who will provide non-transplant care for the subject.
8. Agrees to maintain a stable regimen including weight loss, exercise, medications to control lipids and glucose, and vitamin E therapy if already prescribed, during participation in the study

Exclusion Criteria:

1. Unable to take multiple capsules orally.
2. Alcohol consumption of greater than an average of one drink per day for women and two drinks per day for men.
3. Hemochromatosis.
4. Hepatic encephalopathy.
5. Compromised immune system (e.g. primary immune disorders or clinical immunosuppression due to a medical condition or medication e.g. taking oral prednisone >20 mg a day or prednisone-equivalent)
6. Receipt of systemic non-topical antibiotic therapy within 14 days of treatment day 1.
7. History of use of an investigational drug within 90 days prior to the screening visit.
8. Positive results for active HIV, Hepatitis B, or Hepatitis C infections.
9. Current history for active states of Inflammatory bowel disease, Irritable bowel syndrome, microscopic colitis, celiac disease, short gut syndrome, colostomy, colectomy, gastrointestinal fistulae or strictures.
10. History of significant uncontrolled systemic disease that in the opinion of the study investigator could interfere with study participation and/or objectives.
11. Life expectancy of < 1 year.
12. In the opinion of investigator, subject for any reason, should be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active group; Patients with NAFLD will receive orally fecal microbiota capsules from healthy donors	Drug: PRIM-DJ2727; administration orally
PLACEBO_COMPARATOR: Placebo group; Placebo capsules will be identical to the active capsules, but not contain intestinal bacteria	Drug: Placebo; administration orally placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index	The Shannon diversity index is used to characterize species diversity in a community. Shannon's index accounts for both abundance and evenness of the species present. A high index value would represent a diverse and equally distributed community, and lower values represent a less diverse community. A value of 0 would represent a community with just one species. Typical values are generally between 1.5 and 3.5.	10 months
Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant		10 months
Number of Participants With an Increase in Flora Diversity in Fecal Samples		10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut motility	Changes in gut motility will be determined using Smart Pill (if completed successfully pre and post treatment) measuring gut motility	6 months
Monitor subjects' health information	The SF-36 will be administered at enrollment, follow-up clinic visits at Week 13 and 9 month, and early termination visit. Rapid Eating Assessment for Patients (REAP) is to help quickly assess diet and physical activity of individuals. In addition, subjects will be asked to maintain a paper diary recording number of BM per day and type of each BM after enrollment. Information such as hospitalizations or mortality from any cause will be collected as part of the health outcomes assessment throughout this study.	10 months

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2023
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (ACTUAL): May 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: HSC-SPH-19-1126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No