Back to resultsA Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis
Primary Purpose
Progressive Multiple Sclerosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tauroursodeoxycholic Acid
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Progressive Multiple Sclerosis
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
Sites / Locations
- Johns Hopkins University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TUDCA Treatment
Placebo oral capsule
Arm Description
Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.
Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.
Outcomes
Primary Outcome Measures
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.
Number of Total Treatment-related Adverse Events
Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT03423121
First Posted
January 12, 2018
Last Updated
April 10, 2023
Sponsor
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT03423121
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
June 19, 2018 (Actual)
Primary Completion Date
April 28, 2022 (Actual)
Study Completion Date
July 5, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TUDCA Treatment
Arm Type
Experimental
Arm Description
Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks.
Arm Title
Placebo oral capsule
Arm Type
Placebo Comparator
Arm Description
Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
Tauroursodeoxycholic Acid
Other Intervention Name(s)
Taurolite
Intervention Description
Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Participants will be given four capsules of the placebo twice daily.
Primary Outcome Measure Information:
Title
Number of Participants With at Least One Treatment-related Adverse Event
Description
Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.
Time Frame
16 weeks
Title
Number of Total Treatment-related Adverse Events
Description
Safety and tolerability will be assessed based on treatment-related adverse events in the two arms.
Time Frame
16 weeks
Title
Incidence of Treatment-related Adverse Events (AE)
Description
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.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Change in Fasting Bile Acid Levels in Plasma
Description
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.
Time Frame
Baseline to 16 weeks
Title
Change in Microbiome Alpha-diversity Measured by Shannon Index at the End of the Study
Description
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.
Time Frame
Baseline to 16 weeks
Title
Change in Flow Cytometric Assessments of Peripheral Blood Mononuclear Cells (PBMCs)
Description
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.
Time Frame
Baseline to 16 weeks
Title
Change in Quality of Life Based on Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument
Description
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.
Time Frame
Baseline to 16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pavan Bhargava, MBBS, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis
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