A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis

• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: January 12, 2018
• First Posted Date: February 6, 2018
• Last Update Posted Date: August 7, 2018
• Actual Study Start Date: June 19, 2018
• Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2018)

Incidence of Treatment-related adverse events [ Time Frame: 16 weeks ]

Safety and tolerability will be assessed based on treatment-related adverse events in the two arms

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03423121 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: January 30, 2018)

• Metabolomics [ Time Frame: Baseline to 16 weeks ]
  Change in fasting bile acid levels in plasma.
• Gut microbiota [ Time Frame: Baseline to 16 weeks ]
  Change in composition of the gut microbiota assessed using shot-gun metagenomic sequencing in first morning stool specimen.
• Immunophenotyping [ Time Frame: Baseline to 16 weeks ]
  Change in flow cytometric assessments of peripheral blood mononuclear cells.
• Quality of Life [ Time Frame: Baseline to 16 weeks ]
  Change in physical and mental health scores as assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54) instrument. 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis
• Official Title: A Phase 1/2 Trial of Tauroursodeoxycholic Acid Supplementation in Progressive MS Patients
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Progressive Multiple Sclerosis

Intervention

• Drug: Tauroursodeoxycholic Acid
  Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules.
  Other Name: Taurolite
• Drug: Placebo oral capsule
  Participants will be given four capsules of the placebo twice daily.

Study Arms

• Experimental: TUDCA Treatment
  Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.
  Intervention: Drug: Tauroursodeoxycholic Acid
• Placebo Comparator: Placebo oral capsule
  Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.
  Intervention: Drug: Placebo oral capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 30, 2018): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2020
• Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jesse Ritter, MHS; 410-502-2488; jritte15@jhmi.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03423121
• Other Study ID Numbers: IRB00144766
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University
• Collaborators: Not Provided

Investigators

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

• PRS Account: Johns Hopkins University
• Verification Date: August 2018