RECRUITING

The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) Trial

Conditions

Liver Diseases Liver Failure Cirrhosis, Liver

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) Trial

Quick Facts

Study Start:2025-08-04

Study Completion:2028-02-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06871111

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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	* 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. * 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. * 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. * Patients with delayed gastrointestinal motility as evidenced by ≤ 2 bowel movements per week at the time of enrollment. * Patients who are allergic to both ampicillin/sulbactam and meropenem. * These are the two empiric antibiotic therapies that every strain is susceptible to. * If a patient is allergic to only one of these medications, they may still be approached for enrollment. * A history of allergy to any of the investigational products/components. * Patients with liver disease from Hepatitis C. * Patients with existing inflammatory arthritis. * History of total colectomy. * Patients who do not intend to continue their care on a routine basis at the University of Chicago beyond 6 months from the time of enrollment. * Patients with untreated psychiatric conditions, including illicit substance use disorders, that may interfere with reliable follow-up. * Unable to participate based on medical judgement of the care team. * Special populations: * Women of childbearing age will have a: * Negative serum pregnancy test at screening * Use a medically acceptable and highly effective method of birth control for at least 6 weeks following completion of treatment. * Another investigational drug or LBP: * Prior use will be permitted; * Concurrent use will preclude enrollment; * Use will be restricted for the duration of the study (12 months after commensal consortia completion) * Patients who are prescribed ACE-inhibitors and receive a consortium containing C. comes will receive more frequent blood pressure monitoring. * Patients who are prescribed metformin will require either: * Switch to another medication for diabetes control; or * More frequent Vitamin B12 monitoring at 1, 3, 6, and 12 months of enrollment. * If a Vitamin B12 deficiency is discovered, it will be repleted as clinically indicated.

Inclusion Criteria

Exclusion Criteria

* 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

* 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.
* 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.
* 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.
* Patients with delayed gastrointestinal motility as evidenced by ≤ 2 bowel movements per week at the time of enrollment.
* Patients who are allergic to both ampicillin/sulbactam and meropenem.
* These are the two empiric antibiotic therapies that every strain is susceptible to.
* If a patient is allergic to only one of these medications, they may still be approached for enrollment.
* A history of allergy to any of the investigational products/components.
* Patients with liver disease from Hepatitis C.
* Patients with existing inflammatory arthritis.
* History of total colectomy.
* Patients who do not intend to continue their care on a routine basis at the University of Chicago beyond 6 months from the time of enrollment.
* Patients with untreated psychiatric conditions, including illicit substance use disorders, that may interfere with reliable follow-up.
* Unable to participate based on medical judgement of the care team.
* Special populations:
* Women of childbearing age will have a:
* Negative serum pregnancy test at screening
* Use a medically acceptable and highly effective method of birth control for at least 6 weeks following completion of treatment.
* Another investigational drug or LBP:
* Prior use will be permitted;
* Concurrent use will preclude enrollment;
* Use will be restricted for the duration of the study (12 months after commensal consortia completion)
* Patients who are prescribed ACE-inhibitors and receive a consortium containing C. comes will receive more frequent blood pressure monitoring.
* Patients who are prescribed metformin will require either:
* Switch to another medication for diabetes control; or
* More frequent Vitamin B12 monitoring at 1, 3, 6, and 12 months of enrollment.
* If a Vitamin B12 deficiency is discovered, it will be repleted as clinically indicated.

Contacts and Locations

Study Contact

Matthew A Odenwald, MD, PhD

CONTACT

773-702-6331

matthew.odenwald@uchicagomedicine.org

Christopher Lehmann, MD

CONTACT

773.834.6015

Study Locations (Sites)

The University of Chicago Medical Center

Chicago, Illinois, 60637

United States

Collaborators and Investigators

Sponsor: University of Chicago

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-04

Study Completion Date2028-02-04

Study Record Updates

Study Start Date2025-08-04

Study Completion Date2028-02-04

Terms related to this study

Additional Relevant MeSH Terms

Liver Diseases
Liver Failure
Cirrhosis, Liver