Prebiotic vs Probiotic in Multiple Sclerosis (MS)

Prebiotic and Probiotic Treatment Trial in Multiple Sclerosis

This is a randomized crossover-designed study to explore the immunologic effects of Prebiotics, as opposed to direct supplementation with beneficial bacteria (Probiotics) in the immune system of patients with MS and Clinically Isolated Syndrome (CIS). Eligible patients will take 6 weeks of two different supplements - Prebiotics and Probiotics. Participants will be randomly assigned to take either of two agents for 6 weeks as their first supplement. Then, participants enter a 6-week washout period. After the washout period, participants will take the second supplement for 6 weeks. After taking the second supplement, participants will have a 6-week washout period.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Clinically Isolated Syndrome (CIS)
• Intervention / Treatment: Dietary supplement: Prebiotics (Prebiotin Prebiotic Fiber Stick Pac); Dietary supplement: Probiotics (Visbiome®)

Detailed Description

Soluble fibers (prebiotics) are fermented by beneficial bacteria (probiotics) in the colon to produce short-chain fatty acids (SCFAs) which are the main source of nutrition for the cells in the gut. It has been reported that the fermentable fiber inulin and SCFAs may exert some beneficial effects including anti-inflammatory effect on the immune system. To date, the effect of supplementation with fermentable dietary fiber, such as prebiotics in patients with Multiple Sclerosis (MS) has not been investigated.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rebecca Farber, MD; Phone Number: 212-305-6876; Email: mscenter_neuro@cumc.columbia.edu
• Study Contact Backup: Name: Kaho Onomichi, MS; Phone Number: 212-305-9155; Email: ko2418@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Kaho Onomichi, MS; Phone Number: 212-305-9155; Email: ko2418@cumc.columbia.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Recruiting
      • University of Pittsburg
      • Contact: Zongqi Xia, MD
      • Contact: Wen Zhu; Email: w.zhu@pitt.edu
      • Principal Investigator: Zongqi Xia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (age 18 or older) diagnosed with MS (Relapsing-remitting type) or CIS and recruited within 10 years of symptom onset, and
• Adult patients receiving anti-CD20 therapy (rituximab or ocrelizumab) who have received at least one cycle at the time of recruitment

Exclusion Criteria:

• Active relapse within 3 months of enrollment
• Steroid use within 4 weeks of enrollment
• Antibiotics use within 3 months of enrollment
• Daily pre or prebiotic use within 3 months of enrollment
• Diagnosed with any of the autoimmune disorders: Rheumatoid Arthritis, Lupus, Celiac disease, Vitiligo, Psoriasis, Psoriatic Arthritis, Hashimoto's Thyroiditis, Graves' Disease, Sjogren's syndrome, Type 1 Diabetes, Scleroderma, Crohn's Disease, Ulcerative Colitis, Alopecia Areata.
• Had surgery of the GI tract in the last 5 years (with the exception of cholecystectomy and appendectomy)
• Had a major bowel resection
• Prior use of any of the following drugs: Mycophenolate/Cellcept, Cyclophosphamide/Cytoxan, Methotrexate/Novantrone, Azathioprine/Imuran, Cladribine/Leustatin/Mavenclad, Daclizumab/Zenepax, Alemtuzumab/Campath/Lemtrada

• Have any of the following active uncontrolled gastrointestinal (GI) illnesses:

  1. Crohn's disease, ulcerative colitis, indeterminate colitis
  2. Irritable bowel syndrome: moderate-severe
  3. Persistent or chronic diarrhea of unknown etiology
  4. Severe Chronic constipation or difficulties with defecation
  5. Persistent, infectious gastroenteritis, colitis or gastritis
  6. Clostridium difficile infection (recurrent)
  7. Gastric or intestinal ulcerations/GI bleeding
  8. Gastrointestinal or colonic malignancy: polyps, masses, dysplasia or cancer
• Active use of bismuth subsalicylate-containing products
• Currently pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Prebiotic/ Probiotic; These subjects will be assigned to first receive prebiotics (Prebiotin Prebiotic Fiber Stick Pac) for 6 weeks. Then after a 6 week wash-out period, subjects will take probiotics (Visbiome®) for 6 weeks (followed again by a 6 week washout period).	Dietary supplement: Prebiotics (Prebiotin Prebiotic Fiber Stick Pac); Commercially available Prebiotin Prebiotic. 2 packets (Inulin 4000 mg), Twice Daily (Total of 16 g Daily); Dietary supplement: Probiotics (Visbiome®); Commercially available Probiotics Visbiome extra strength, which is a combination of live lactic acid bacteria probiotics that have been cultivated, freeze-dried and mixed in very high concentrations. 2 packets (450 billion CFU), Twice Daily (Total of 3,600 billion Daily)
Other: Probiotic/ Prebiotic; These subjects will be assigned to first receive probiotics (Visbiome®) for 6 weeks. Then after a 6 week wash-out period, subjects will take (Prebiotin Prebiotic Fiber Stick) for 6 weeks (followed again by a 6 week washout period).	Dietary supplement: Prebiotics (Prebiotin Prebiotic Fiber Stick Pac); Commercially available Prebiotin Prebiotic. 2 packets (Inulin 4000 mg), Twice Daily (Total of 16 g Daily); Dietary supplement: Probiotics (Visbiome®); Commercially available Probiotics Visbiome extra strength, which is a combination of live lactic acid bacteria probiotics that have been cultivated, freeze-dried and mixed in very high concentrations. 2 packets (450 billion CFU), Twice Daily (Total of 3,600 billion Daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peripheral Blood Mononuclear Cells (pBMCs)	Measure the number of differentially expressed probe sets in the pBMCs post-supplementation, as compared to subject baseline. Probe sets will count as differentially expressed based on a threshold of pBH <0.05 and a Fold Change (FC) > ±2.	Up to 24 weeks
Change in Serum Neurofilament Light Concentration	Change in serum neurofilament light concentration post-supplementation as compared to baseline. Serum neurofilament light (NfL) will be measured in terms of pg/ML.	Up to 24 weeks
Change in relative abundance of gut microbiome	Changes in the gut microbiota in stool samples will be assessed as percent relative abundance at the genus level post supplementation as compared to baseline. Gut microbiota will be identified by extracting bacterial DNA from stool samples and performing metagenome shotgun sequencing.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Fatigue Impact Scale	Modified Fatigue Impact Scale assesses fatigue effects in terms of physical, cognitive, and psychosocial functioning. The total core ranges from 0 - 20 (5 item version). Higher scores suggest a greater impact of fatigue on a patient's activities.	Up to 24 weeks
Bowel Control Scale	Bowel Control Scale measures the impact of bowel control on lifestyle. The total score range from 0 - 26 (5 item version). Higher scores indicate greater bowel control issues.	Up to 24 weeks
Patient Determined Disease Steps	Patient Determined Disease Steps assesses disability and walking ability in MS patients. Scores range from 0 (normal) to 8 (bedridden).	Up to 24 weeks
Multiple Sclerosis Rating Scale	Multiple Sclerosis Rating Scale - Revised evaluates functional status to identify disability in domains other than walking. Scores range from 0 (normal status) to 4 (severe disability).	Up to 24 weeks
Patient Health Questionnaire	Patient Health Questionnaire helps identify symptoms that could be related to depression. The total score ranges from 0 (None) to 27 (Severe).	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Multiple Sclerosis Society; Exegi Pharma
• Investigators: Principal Investigator: Rebecca Farber, MD, Columbia University; Principal Investigator: Zongqi Xia, MD, University of Pittsburgh (Collaborator Site)

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Probiotics; Gut microbiome; Prebiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: AAAR9614

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No