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Evaluate the Efficacy, Safety and Tolerability of Fecal Microbiota Transfer for the Treatment of Patients With Nonalcoholic Steatohepatitis (EMOTION)

Primary Purpose

Patients With Nonalcoholic Steatohepatitis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Group 1 or Experimental group
Group 2 or Control group
Sponsored by
Instituto de Investigación Marqués de Valdecilla
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patients With Nonalcoholic Steatohepatitis focused on measuring MetEH: metabolic hepatic steatosis, NASH nonalcoholic steatohepatitis, TMF: fecal microbiota transplantation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients of both genders aged between 18 and75 years old (both included). Body mass index (BMI) <40 kg/m2. Histological diagnosis of NASH, accepted by EASL and AASLD , from a liver biopsy obtained up to 24 weeks prior to the signing of the informed consent. NASH histologic activity score (NAS) ≥ 4, with a score of 1 or more in each subcomponent (steatosis, lobular inflammation, and liver cell ballooning). Histologic evidence of stage 1 fibrosis (with perisinusoidal or portal fibrosis), stage 2 (perisinusoidal and portal/periportal fibrosis), or stage 3 (bridging fibrosis) as defined by the NASH CRN fibrosis score. Exclusion Criteria: Evidence of other type of liver disease. History of high alcohol intake (daily consumption > 30 g/day for men and > 20 g/day for women). Weight change of more than 5% in the 3 months prior to screening. Subjects with HbA1c> 9.5%. For subjects with an HbA1c> 9.5% at the screening visit, a repeat test may be performed within the screening window. A repeated result of HbA1c> 9.5% will result in exclusion. Diabetic patients with: Insulin treatment. Changes in antidiabetic medication in the 4 months prior to liver biopsy according to the following conditions: Modification of the dose of treatment with glucagon agonists type 1 (GLP-1). Implementation of treatment with a new antidiabetic. History of bariatric surgery. Cirrhosis. Portal thrombosis. Known or suspected hepatocellular carcinoma. Clinically significant gastrointestinal, cardiovascular, neurological, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease, as determined by the investigator. An estimated glomerular filtration rate (eGFR) <45 ml / min / 1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method). Medical conditions that decrease life expectancy to less than 2 years, including cancer. Presence of an inherited or acquired immunodeficiency. Diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis, microscopic colitis), active irritable bowel syndrome (within the last 2 years according to Rome IV criteria), celiac disease not well controlled with a gluten-free diet, active gastroparesis, toxic megacolon. Major intra-abdominal surgery in the 2 months prior to randomization of the patient in the study. Antibiotic intake in the 8 weeks prior to the screening date. Probiotic/prebiotic/marketed synbiotic intake in the 4 weeks prior to the screening date. Pregnancy or lactation. Any other condition that, in the opinion of the investigator, could prevent or hinder compliance. Use of medication with potential steatogenic effect (corticosteroids, valproic acid, amiodarone and/or tamoxifen) within the 6 months prior to the first dose of study drug.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Group 1 or Experimental group

    Group 2 or Control group

    Arm Description

    treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months (4 maintenance doses).

    treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months for 12 months (4 maintenance doses)

    Outcomes

    Primary Outcome Measures

    Proportion of patients with improvement of fat fraction by proton density by MRI and no worsening of activity or fibrosis.
    Proportion of patients with resolution of NASH without worsening of fibrosis.
    Proportion of patients with no worsening of fibrosis or activity.
    number of adverse events (AEs), serious AEs, AEs resulting in discontinuation of study treatment, AEs of special interest, and changes in vital signs and laboratory values

    Secondary Outcome Measures

    Proportion of patients with improvement (at least one point) in lobular swelling and/or ballooning without worsening of fibrosis.
    NAFLD Fibrosis score
    Changes in weight, BMI.
    Changes in systolic and diastolic blood pressure, lipid profile, carotid ultrasound.
    Changes in the quality of life questionnaire specific to chronic liver disease due to NAFLD.

    Full Information

    First Posted
    September 21, 2022
    Last Updated
    November 14, 2022
    Sponsor
    Instituto de Investigación Marqués de Valdecilla
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05622526
    Brief Title
    Evaluate the Efficacy, Safety and Tolerability of Fecal Microbiota Transfer for the Treatment of Patients With Nonalcoholic Steatohepatitis
    Acronym
    EMOTION
    Official Title
    Randomized, Double-blind, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Fecal Microbiota Transfer by Capsules vs. Placebo for the Treatment of Patients With Nonalcoholic Steatohepatitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2023 (Anticipated)
    Primary Completion Date
    November 1, 2024 (Anticipated)
    Study Completion Date
    March 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Instituto de Investigación Marqués de Valdecilla

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The EMOTION study is a multicentric, double-blind, controlled, parallel-group, phase IIa randomized Clinical trial to evaluate the efficacy, safety and tolerability of TMF capsules for the treatment of patients with NASH. The clinical trial has two stages: Screening phase with a duration of 12 weeks to classify patients based on lifestyle modifications. Treatment phase where patients will be randomized and stratified 2:1 to treatment: Experimental for n=64 patients. Placebo control for n=32 patients.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Patients With Nonalcoholic Steatohepatitis
    Keywords
    MetEH: metabolic hepatic steatosis, NASH nonalcoholic steatohepatitis, TMF: fecal microbiota transplantation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Masking Description
    Double blind
    Allocation
    Randomized
    Enrollment
    96 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1 or Experimental group
    Arm Type
    Experimental
    Arm Description
    treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months (4 maintenance doses).
    Arm Title
    Group 2 or Control group
    Arm Type
    Placebo Comparator
    Arm Description
    treatment with an initial dose of 24 oral capsules of MBK-01 and a maintenance dose of 12 oral capsules of MBK-01 every 3 months for 12 months (4 maintenance doses)
    Intervention Type
    Drug
    Intervention Name(s)
    Group 1 or Experimental group
    Intervention Description
    Capsules of fecal microbiota transplantation
    Intervention Type
    Other
    Intervention Name(s)
    Group 2 or Control group
    Intervention Description
    capsules of placebo
    Primary Outcome Measure Information:
    Title
    Proportion of patients with improvement of fat fraction by proton density by MRI and no worsening of activity or fibrosis.
    Time Frame
    72 weeks
    Title
    Proportion of patients with resolution of NASH without worsening of fibrosis.
    Time Frame
    72 weeks
    Title
    Proportion of patients with no worsening of fibrosis or activity.
    Time Frame
    72 weeks
    Title
    number of adverse events (AEs), serious AEs, AEs resulting in discontinuation of study treatment, AEs of special interest, and changes in vital signs and laboratory values
    Time Frame
    72 weeks
    Secondary Outcome Measure Information:
    Title
    Proportion of patients with improvement (at least one point) in lobular swelling and/or ballooning without worsening of fibrosis.
    Time Frame
    72 weeks
    Title
    NAFLD Fibrosis score
    Time Frame
    72 weeks
    Title
    Changes in weight, BMI.
    Time Frame
    72 weeks
    Title
    Changes in systolic and diastolic blood pressure, lipid profile, carotid ultrasound.
    Time Frame
    72 weeks
    Title
    Changes in the quality of life questionnaire specific to chronic liver disease due to NAFLD.
    Time Frame
    72 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients of both genders aged between 18 and75 years old (both included). Body mass index (BMI) <40 kg/m2. Histological diagnosis of NASH, accepted by EASL and AASLD , from a liver biopsy obtained up to 24 weeks prior to the signing of the informed consent. NASH histologic activity score (NAS) ≥ 4, with a score of 1 or more in each subcomponent (steatosis, lobular inflammation, and liver cell ballooning). Histologic evidence of stage 1 fibrosis (with perisinusoidal or portal fibrosis), stage 2 (perisinusoidal and portal/periportal fibrosis), or stage 3 (bridging fibrosis) as defined by the NASH CRN fibrosis score. Exclusion Criteria: Evidence of other type of liver disease. History of high alcohol intake (daily consumption > 30 g/day for men and > 20 g/day for women). Weight change of more than 5% in the 3 months prior to screening. Subjects with HbA1c> 9.5%. For subjects with an HbA1c> 9.5% at the screening visit, a repeat test may be performed within the screening window. A repeated result of HbA1c> 9.5% will result in exclusion. Diabetic patients with: Insulin treatment. Changes in antidiabetic medication in the 4 months prior to liver biopsy according to the following conditions: Modification of the dose of treatment with glucagon agonists type 1 (GLP-1). Implementation of treatment with a new antidiabetic. History of bariatric surgery. Cirrhosis. Portal thrombosis. Known or suspected hepatocellular carcinoma. Clinically significant gastrointestinal, cardiovascular, neurological, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease, as determined by the investigator. An estimated glomerular filtration rate (eGFR) <45 ml / min / 1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] method). Medical conditions that decrease life expectancy to less than 2 years, including cancer. Presence of an inherited or acquired immunodeficiency. Diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis, microscopic colitis), active irritable bowel syndrome (within the last 2 years according to Rome IV criteria), celiac disease not well controlled with a gluten-free diet, active gastroparesis, toxic megacolon. Major intra-abdominal surgery in the 2 months prior to randomization of the patient in the study. Antibiotic intake in the 8 weeks prior to the screening date. Probiotic/prebiotic/marketed synbiotic intake in the 4 weeks prior to the screening date. Pregnancy or lactation. Any other condition that, in the opinion of the investigator, could prevent or hinder compliance. Use of medication with potential steatogenic effect (corticosteroids, valproic acid, amiodarone and/or tamoxifen) within the 6 months prior to the first dose of study drug.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Javier Crespo
    Phone
    942315515
    Email
    javiercrespo1991@gmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Paula Iruzubieta
    Phone
    942315515
    Email
    paula.iruzubieta@scsalud.es

    12. IPD Sharing Statement

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