Progressive Multiple SclerosisPhase 1/2NCT03423121
A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis
A Phase 1/2 study testing Tauroursodeoxycholic Acid in people with Progressive Multiple Sclerosis, run by Johns Hopkins University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Progressive Multiple Sclerosis
- What is being tested?
- Tauroursodeoxycholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2018to 5 Jul 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1/2 Trial of Tauroursodeoxycholic Acid Supplementation in Progressive MS Patients
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
- Being tested
- Tauroursodeoxycholic Acid, Placebo oral capsule
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tauroursodeoxycholic AcidDrug
Also called Taurolite
Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules.
Placebo oral capsuleDrug
Participants will be given four capsules of the placebo twice daily.
| Study group | Role | What they receive |
|---|---|---|
| TUDCA Treatment | Experimental | Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. Receives: Drug: Tauroursodeoxycholic Acid |
| Placebo oral capsule | Placebo comparator | Placebo oral capsule four capsules by mouth, twice daily for 16 weeks. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 16 weeks
Secondary outcomes (4)
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.
Measured: Baseline to 16 weeks
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.
Measured: Baseline to 16 weeks
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.
Measured: Baseline to 16 weeks
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.
Measured: Baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start19 Jun 2018
- Primary completion28 Apr 2022
- Study completion5 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pavan Bhargava, MBBS, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03423121
- Sponsor's protocol ID
- IRB00144766
- Status last verified
- Apr 2023
- First submitted
- 12 Jan 2018
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ladakis DC, Harrison KL, Smith MD, Solem K, Gadani S, Jank L, Hwang S, Farhadi F, Dewey BE, Fitzgerald KC, Sotirchos ES, Saidha S, Calabresi PA, Bhargava P. Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease. Med. 2025 Mar 14;6(3):100522. doi: 10.1016/j.medj.2024.09.011. Epub 2024 Oct 23.
PubMed 39447576
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of Tauroursodeoxycholic Acid Supplementation in Progressive MS Patients
- ClinicalTrials.gov ID
- NCT03423121
- Acronym / sponsor ID
- IRB00144766
- Conditions
- Progressive Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 19 Jun 2018 (actual)
- Primary completion
- 28 Apr 2022 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 6 Feb 2018 (actual)
- Results
- Posted 3 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TUDCA Treatment | Experimental | Drug: Tauroursodeoxycholic AcidTauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. |
| Placebo oral capsule | Placebo comparator | Drug: Placebo oral capsulePlacebo oral capsule four capsules by mouth, twice daily for 16 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tauroursodeoxycholic AcidAlso: TauroliteParticipants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules. | Drug | TUDCA Treatment |
| Placebo oral capsuleParticipants will be given four capsules of the placebo twice daily. | Drug | Placebo oral capsule |
Primary outcome
Number of Participants With at Least One Treatment-related Adverse Event
Time frame: 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
Time frame: 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)
Time frame: 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.
4 secondary outcomes
Change in Fasting Bile Acid Levels in Plasma
Time frame: Baseline to 16 weeks
Change in Microbiome Alpha-diversity Measured by Shannon Index at the End of the Study
Time frame: Baseline to 16 weeks
Change in Flow Cytometric Assessments of Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: Baseline to 16 weeks
Change in Quality of Life Based on Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument
Time frame: Baseline to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39447576Ladakis DC, Harrison KL, Smith MD, Solem K, Gadani S, Jank L, Hwang S, Farhadi F, Dewey BE, Fitzgerald KC, Sotirchos ES, Saidha S, Calabresi PA, Bhargava P. Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease. Med. 2025 Mar 14;6(3):100522. doi: 10.1016/j.medj.2024.09.011. Epub 2024 Oct 23.
- Individual participant dataSharing planned: No
Related trials for Progressive Multiple Sclerosis
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
RecruitingPhase 3
A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis
Multiple Sclerosis (MS) Primary Progressive
RecruitingPhase 2
A Phase 2a Study of SUN-627 in Participants With Non-Active Secondary Progressive and Primary Progressive Multiple Sclerosis (SPMS/PPMS)
Primary Progressive Multiple Sclerosis, Primary Progressive MS
RecruitingPhase 4
A Study of Ocrelizumab Administered Subcutaneously in Participants With Multiple Sclerosis Who Switch From an Approved Anti-CD20 Therapy
Multiple Sclerosis
RecruitingObservational study
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Progressive Multifocal Leukoencephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pavan Bhargava, MBBS, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tauroursodeoxycholic Acid in people with Progressive Multiple Sclerosis, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With at Least One Treatment-related Adverse Event (time frame: 16 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03423121, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.