A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis

Progressive Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03423121
• Other study ID #: IRB00144766
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 19, 2018
• Est. completion date: July 5, 2022

Study information

• Verified date: April 2023
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: July 5, 2022
• Est. primary completion date: April 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Progressive Multiple Sclerosis
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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