The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) Trial

NCT06871111 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB24-0560
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) trial is a single center prospective adaptive phase 1b clinical trial in patients who are hospitalized with complications of liver disease and have low fecal metabolite levels (butyrate and deoxycholic acid). The study intervention is 1 of 9 novel live Commensal Consortia each containing eight commensal bacterial strains derived from healthy donors. The primary objective of the study is to determine safety and tolerability of Commensal Consortia administration.

Conditions

Liver Diseases; Liver Failure; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (2)

• The incidence of adverse events (AEs and SAEs) attributable to the Commensal Consortia

  Adverse events will be monitored for 1 year after Commensal Consortium administration using in-person contact, telephone calls and/or Patient-Reported Outcomes

  Day 1- Month 12

• Patient-Reported Outcomes Measurement Information System (PROMIS) scores after Commensal Consortia administration

  Tolerability will be assessed for 1 year after Commensal Consortium administration through completion of PROMIS surveys. Surveys will be obtained by the investigators using in-person contact, telephone calls and/or Patient-Reported Outcomes.

  Day 1- Month 12

Secondary Outcomes (1)

• The presence of administered bacterial strains in fecal samples

  Day 1- Month 12

Other Outcomes (1)

• Metabolite concentrations in fecal samples

  Day 1- Month 12

Study Arms (9)

Commensal Consortium A

EXPERIMENTAL

Stage 1: 1st 8 patients enrolled will receive Consortium A. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium B1

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium B2

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium C1

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium C2

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium D1

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium D2

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 8 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium E1

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Commensal Consortium E2

EXPERIMENTAL

Stage 2: Based on fecal metagenomic and metabolomic data from Stage 1, subjects may be assigned to this Commensal Consortium. This consortium contains 7 different organisms.

Biological: Commensal Bacteria Strains

Interventions

Commensal Bacteria Strains BIOLOGICAL

7 doses containing 7 capsules will be administered over 7-10 days

Also known as: Lyophilized live commensal bacterial strains (Live Biotherapeutic Product), Commensal Consortium

Commensal Consortium A; Commensal Consortium B1; Commensal Consortium B2; Commensal Consortium C1; Commensal Consortium C2; Commensal Consortium D1; Commensal Consortium D2; Commensal Consortium E1; Commensal Consortium E2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Diagnosis of liver disease, liver failure, and/or cirrhosis
• All patients will be hospitalized and have a hepatology consult in place.
• They will be identified as having liver disease, liver failure, and/or cirrhosis based on a combination of at least one of the following:
• Labs demonstrating elevated liver chemistries (AST and ALT), elevated serum bilirubin levels, prolonged INR, or radiologic evidence of cirrhosis (e.g. nodular liver contour);
• Liver biopsy results; and/or
• Clinical or radiologic evidence of portal hypertension (e.g. splenomegaly, known varices, ascites, or hepatic venous pressure gradient ≥ 10mmHg).
• All diagnoses will be confirmed by the attending hepatologist's interpretation and consult note attestation.
• Admitted to the hospital for hepatic decompensation
• MELD score ≤ 30 at time of enrollment
• Subject has ≤ 700µM butyrate and ≤ 10µM deoxycholate in fecal sample

You may not qualify if:

• MELD score \>30 at time of enrollment
• Patients receiving any antibiotics for treatment of an infection.
• Chronic or prophylactic antibiotic administration other than rifaximin, ciprofloxacin, or trimethoprim-sulfamethoxazole.
• Rifaximin will be either temporarily held or switched to another non-antibiotic therapy (e.g. lactulose or sodium benzoate) during the treatment phase of the trial. Potential subjects in whom the treating hepatologist deem it unsafe to pause or switch from Rifaximin therapy during the 7-10 day treatment phase will be excluded from the study.
• Patients who are currently admitted to the intensive care unit for vasoactive support or mechanical ventilation.
• Patients meeting the North American Consortia for Study of End Stage Liver Disease (NACSELD) criteria for acute-on-chronic liver failure (ACLF) with ≥ 2 organ failures by NACSELD-ACLF criteria at time of enrollment.
• Patients with known intestinal barrier dysfunction, including active GI bleeding, enteropathy (including celiac disease), clinically active inflammatory bowel disease (Crohn's or Ulcerative Colitis), ischemic colitis, microscopic colitis, graft versus host disease (GVHD), or gastrointestinal malignancy.
• o Active inflammatory bowel disease (IBD) will be defined based on a combination of:
• Symptoms (diarrhea and/or abdominal pain without another explanation)
• Laboratory evidence of inflammation (e.g. elevated CRP or fecal calprotectin without another explanation); and
• Either radiologic, endoscopic, and/or histologic evidence of active IBD.
• If IBD is suspected, this will be investigated with the general GI consult service prior to approaching for enrollment.
• If patients carry a diagnosis of IBD but do not meet the above criteria, they will be eligible for enrollment unless their IBD is managed with a systemic immunosuppression medication (e.g. anti-TNF-alpha therapy).
• If any form of the above intestinal disorders is suspected, they will be investigated with the general GI consult service prior to approaching for enrollment.
• Profoundly immunocompromised patients, including patients with primary immunodeficiency, solid organ transplant recipients, any history of hematopoietic stem cell transplant (HSCT), ongoing cancer treatment, neutropenia \< 500 cells/mm3, HIV untreated or with CD4 \< 200 cells/mm3, immunosuppressive medications, including rituximab, anti-cytokine therapy, anti-rejection medications, chronic corticosteroids (a dose ≥ 20mg of prednisone daily for ≥ 1 month), biologic therapy for autoimmune condition.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Liver Diseases; Liver Failure; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Digestive System Diseases; Hepatic Insufficiency; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Matthew A Odenwald, MD, PhD

CONTACT

773-702-6331; matthew.odenwald@uchicagomedicine.org

Christopher Lehmann, MD

CONTACT

773.834.6015

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Using adaptive trial design, there is the potential that patients could receive 1 of 9 different 8-member bacterial consortia. After the initial 8 subjects complete treatment with Consortium A, fecal metagenomic and metabolomic information will be used to classify results into 1 of 5 different conditions (Condition 1, 2(i), 2(ii), 2(iii), or 3). The subsequent 16 subjects will be given consortium based on these results. If Consortium A has good engraftment and metabolite production, the following 16 subjects will also be given Consortium A. Otherwise, patients will be given two sub-consortia (B-E), and subjects will be randomized 1:1 into the two sub-consortia.

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: March 11, 2025
• Study Start: August 4, 2025
• Primary Completion (Estimated): August 4, 2027
• Study Completion (Estimated): February 4, 2028
• Last Updated: November 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)