A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis

NCT03423121 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB00144766
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Change in Fasting Bile Acid Levels in Plasma

  Baseline to 16 weeks

• Change in Microbiome Alpha-diversity Measured by Shannon Index at the End of the Study

  Baseline to 16 weeks

• Change in Flow Cytometric Assessments of Peripheral Blood Mononuclear Cells (PBMCs)

  Baseline to 16 weeks

• Change in Quality of Life Based on Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument

  Baseline to 16 weeks

Study Arms (2)

TUDCA Treatment

EXPERIMENTAL

Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.

Drug: Tauroursodeoxycholic Acid

Placebo oral capsule

PLACEBO COMPARATOR

Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.

Drug: Placebo oral capsule

Interventions

Tauroursodeoxycholic Acid DRUG

Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules.

Also known as: Taurolite

TUDCA Treatment

Placebo oral capsule DRUG

Participants will be given four capsules of the placebo twice daily.

Placebo oral capsule

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

ursodoxicoltaurine

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Pavan Bhargava
• Organization: Johns Hopkins University School of Medicine

pbharga2@jhmi.edu

410-614-1522

Study Officials

• Pavan Bhargava, MBBS, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: February 6, 2018
• Study Start: June 19, 2018
• Primary Completion: April 28, 2022
• Study Completion: July 5, 2022
• Last Updated: May 3, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)