A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis

A Phase 1/2 Trial of Tauroursodeoxycholic Acid Supplementation in Progressive MS Patients

This study aims to identify the safety and tolerability of bile acid supplementation in patients with progressive Multiple Sclerosis (MS). Participants will also be assessed for an impact of the bile acid on their immune system and gut microbiome. Half of the participants will receive the bile acid tauroursodeoxycholic acid (TUDCA) and half will receive placebo. The investigators believe participants who take TUDCA will have normalization of blood bile acid levels, a normalization of abnormal immune response and a normalization of the gut microbiome.

Study Overview

• Status: Completed
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Tauroursodeoxycholic Acid; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Progressive MS based on Lublin Criteria
• Low bile acid levels identified using targeted metabolomics analysis
• On the same therapy for the past 6 months and not expected to switch therapy in the next 6 months
• No relapse in the past 3 months

Exclusion Criteria:

• No previous history of liver disease or cholecystectomy
• No stage IV/V chronic kidney disease or other severe metabolic derangements (e.g. poorly controlled thyroid disease or diabetes)
• BMI < 15 kg/m2 and BMI > 40 kg/m2
• Female patients who are pregnant or nursing, or not willing to use contraception
• Chronic antibiotic use
• Corticosteroid treatment within the past 30 days
• Known history of other neuroinflammatory, neurodegenerative or systemic autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TUDCA Treatment; Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.	Drug: Tauroursodeoxycholic Acid; Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules.; Other Names: Taurolite
Placebo Comparator: Placebo oral capsule; Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.	Drug: Placebo oral capsule; Participants will be given four capsules of the placebo twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Treatment-related Adverse Event	Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.	16 weeks
Number of Total Treatment-related Adverse Events	Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.	16 weeks
Incidence of Treatment-related Adverse Events (AE)	Safety and tolerability will be assessed based on treatment-related adverse events in the two arms. AE incidence will be measured as total number of events per 1000 exposure years.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Bile Acid Levels in Plasma	The change of targeted bile acid levels over the course of 16 weeks (duration of the study) is reported. Bile acid levels (ng/mL) were log transformed before analysis to approximate normal distribution. Units are log(levels) per 16 weeks. Values are derived from linear mixed-effects models.	Baseline to 16 weeks
Change in Microbiome Alpha-diversity Measured by Shannon Index at the End of the Study	Change in Shannon index of the gut microbiota between baseline and end of study (16 weeks). Shot-gun metagenomic sequencing in first morning stool specimen was utilized to derive the microbiome composition. Higher values of the index indicate more diversity in the microbial community. The minimum value the Shannon index can take is 0 (no diversity). There is no upper limit to the index.	Baseline to 16 weeks
Change in Flow Cytometric Assessments of Peripheral Blood Mononuclear Cells (PBMCs)	Change in flow cytometric assessments over the course of 16 weeks (duration of the study). Cells are expressed as ratios of their parent types. Units reported as change in the ratio per 16 weeks. Values are derived from linear mixed-effects models.	Baseline to 16 weeks
Change in Quality of Life Based on Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument	Change in physical and mental health scores as assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54) instrument over the course of 16 weeks (duration of the study). This 54-item instrument generates 12 subscales along with two summary scores, and two additional single-item measures. Two summary scores - physical health and mental health - are derived from a weighted combination of scale scores. Higher scores suggest a better quality of life. Scores can range from 0 to 100.	Baseline to 16 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Pavan Bhargava, MBBS, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): July 5, 2022

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Anti-Infective Agents; Antiviral Agents; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodoxicoltaurine
• Other Study ID Numbers: IRB00144766

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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