A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis

Phase 1

Completed

Conditions: Progressive Multiple Sclerosis

Interventions: Drug: Placebo oral capsule
Drug: Tauroursodeoxycholic Acid

Registration Number: NCT03423121

Lead Sponsor: Johns Hopkins University

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo oral capsule	Placebo oral capsule	Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.
TUDCA Treatment	Tauroursodeoxycholic Acid	Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With at Least One Treatment-related Adverse Event	16 weeks	Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.
Number of Total Treatment-related Adverse Events	16 weeks	Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.
Incidence of Treatment-related Adverse Events (AE)	16 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Quality of Life Based on Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument	Baseline to 16 weeks	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.
Change in Microbiome Alpha-diversity Measured by Shannon Index at the End of the Study	Baseline to 16 weeks	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.
Change in Fasting Bile Acid Levels in Plasma	Baseline to 16 weeks	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.
Change in Flow Cytometric Assessments of Peripheral Blood Mononuclear Cells (PBMCs)	Baseline to 16 weeks	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.