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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TUDCA Treatment | Experimental | Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. |
|
| Placebo oral capsule | Placebo Comparator | Placebo oral capsule four capsules by mouth, twice daily for 16 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tauroursodeoxycholic Acid | Drug | Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pavan Bhargava, MBBS, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39447576 | Derived | 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. |
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Out of the 59 people that got enrolled, four (4) were lost to follow-up and did not come for a baseline visit, while one (1) was not eligible based on the screening visit assessments, ending up with 54 people.
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| ID | Title | Description |
|---|---|---|
| FG000 | TUDCA Treatment | Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. Tauroursodeoxycholic Acid: Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules. |
| FG001 | Placebo Oral Capsule | Placebo oral capsule four capsules by mouth, twice daily for 16 weeks. Placebo oral capsule: Participants will be given four capsules of the placebo twice daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TUDCA Treatment | Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. Tauroursodeoxycholic Acid: Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules. |
| BG001 | Placebo Oral Capsule |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who received at least one dose of the intervention and came back for a follow-up visit. | Posted | Count of Participants | Participants | 16 weeks |
|
16 weeks
All participants who received at least one dose of the intervention and had at least one follow-up visit in order to be evaluated for adverse events were considered at risk.
Two (2) participants in the TUDCA group and five (5) participants in the placebo group were lost to follow-up or withdrew and therefore the number at risk is 26 and 21 for the TUDCA and placebo group, respectively.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TUDCA Treatment | Tauroursodeoxycholic acid (Taurolite) 250 mg four capsules by mouth, twice daily for 16 weeks. Tauroursodeoxycholic Acid: Participants will be given 1 gram of Tauroursodeoxycholic acid twice daily in the form of four 250mg capsules. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment | Patient was hospitalized with cholecystitis and bacteremia; received IV antibiotics and improved; discharged after 4 days; underwent cholecystectomy after 2 months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal cramps | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Pavan Bhargava | Johns Hopkins University School of Medicine | 410-614-1522 | pbharga2@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 11, 2021 | Mar 28, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020528 | Multiple Sclerosis, Chronic Progressive |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C031655 | ursodoxicoltaurine |
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| Placebo oral capsule | Drug | Participants will be given four capsules of the placebo twice daily. |
|
| 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 |
| 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 |
| 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 |
Placebo oral capsule four capsules by mouth, twice daily for 16 weeks. Placebo oral capsule: Participants will be given four capsules of the placebo twice daily. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Placebo oral capsule four capsules by mouth, twice daily for 16 weeks.
Placebo oral capsule: Participants will be given four capsules of the placebo twice daily.
|
|
| 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. | All participants who received at least one dose of the intervention and had at least two measurements of bile acid levels in plasma. | Posted | Mean | 95% Confidence Interval | log(levels[ng/mL]) per 16 weeks | 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. | All participants who received at least one dose of the intervention and returned at least two stool kits were included in the analysis | Posted | Mean | 95% Confidence Interval | score on a scale | 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. | All participants who received at least one dose of the intervention and had at least two blood draws that resulted in PBMC isolation were included in the analysis | Posted | Mean | 95% Confidence Interval | parent cell ratio per 16 weeks | 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. | All participants who received at least one dose of the intervention and completed at least two MSQOL questionnaires were included in the analysis | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline to 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. | All participants who received at least one dose of the intervention and came back for a follow-up visit. | Posted | Number | total treatment-related adverse events | 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. | All participants who received at least one dose of the intervention and came back for a follow-up visit. | Posted | Number | total events per 1000 exposure years | 16 weeks |
|
|
|
| 0 |
| 26 |
| 1 |
| 26 |
| 9 |
| 26 |
| EG001 | Placebo Oral Capsule | Placebo oral capsule four capsules by mouth, twice daily for 16 weeks. Placebo oral capsule: Participants will be given four capsules of the placebo twice daily. | 0 | 21 | 0 | 21 | 7 | 21 |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea/Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Gastroesophageal Reflux | Gastrointestinal disorders | Systematic Assessment |
|
| Increased flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | Systematic Assessment |
|
| Facial rash (left) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Urinary Tract Infection | Renal and urinary disorders | Systematic Assessment |
|
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| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Deoxycholic Acid |
|
| Glycochenodeoxycholic Acid |
|
| Glycocholic Acid |
|
| Glycodeoxycholic Acid |
|
| Glycolithocholic Acid |
|
| Glycoursodeoxycholic Acid |
|
| Lithocholic Acid |
|
| Taurochenodeoxycholic Acid |
|
| Taurocholic Acid |
|
| Taurodeoxycholic Acid |
|
| Taurolithocholic Acid |
|
| Tauroursodeoxycholic Acid |
|
| Ursodeoxycholic Acid |
|