Impact of Tecfidera on Gut Microbiota

NCT ID: NCT02736279

Last Updated: 2016-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-05-31

Study Completion Date

2020-12-31

Brief Summary

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Objectives: Dimethyl fumarate (DMF) therapy may cause a measureable change in bacterial species of the gut. The primary objectives of this study are:

1. Determine whether a measureable change in bacterial species representation follows the institution of DMF.
2. Determine whether a specific pattern of change in the microbiota phylotype with DMF therapy correlates to onset and severity of gastrointestinal disturbances (heartburn, nausea, flatulence, and diarrhea).
3. Determine whether any instability of microbiota phylotype representation persists following the institution of DMF or whether stabilization relates to resolution of gastrointestinal disturbances.
4. Determine whether there is a correlation between a pre-existing functional bowel disorder and development or severity of gastrointestinal disturbances and of peripheral eosinophilia.

Design: Double-blinded, prospective, single-center pilot study.

Patient Population: Individuals 18 years or older, with a confirmed diagnosis of a relapsing form of multiple sclerosis.

Treatment Groups: This study will be an open-label prospective study design with respect to MS immunomodulatory therapy choice. Study group will be defined as subjects with a relapsing form of multiple sclerosis, as defined by the McDonald criteria, choosing to begin DMF therapy.

Detailed Description

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This will be an open-label prospective study design with respect to MS immunomodulatory therapy choice. Study group will be defined as subjects with a relapsing form of multiple sclerosis as defined by the McDonald criteria choosing to begin dimethyl fumarate (DMF) therapy. Blinding of the principal investigator and study subject to microbiota analysis results will be maintained until the planned end of study. Subjects who receive at least one dose of DMF and subsequently discontinue therapy will be invited to complete the study on alternative immunomodulatory therapy or no therapy. Data from subjects who have received at least one dose of DMF and who withdraw early from the study will be included in analysis as last visit carried forward. A goal has been set to enroll 25 subjects for this study.

Gut microbiota will be characterized using a commercial service, Second Genome, utilizing bacterial DNA extraction from stool samples and 16S ribosomal RNA gene amplification, followed by high-throughput sequencing. Taxonomic profiling on the Illumina MiSeq system is cycled to generate paired 250-bp reads in Second Genome's protocols. These longer read lengths provide high-quality full length-reads of the gene to ensure the most accurate classification available through sequencing technologies. Next generation sequencing has emerged as a powerful tool for investigating microbial communities in large sample sets.

Serial stool samples will be collected from each subject, and sent to Second Genome for analysis. The first stool sample will be collected prior to the initial dose of DMF, with subsequent collections at defined time points over the course of the study. A more intensive analysis will focus on the first 12 weeks of treatment, a time during which development and resolution of gastrointestinal side effects typically take place on therapy. Treatment-emergent flushing severity will be recorded during this time using a 5-point Likert scale flushing severity survey. Gastrointestinal (G.I.) symptoms will be assessed using the Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire, a validated, self-administered questionnaire that includes 15 questions, which assess severity of G.I. symptoms using a 7-point Likert scale in five domains: indigestion, diarrhea, constipation, abdominal pain and reflux. The severity of symptoms reported in the GSRS increases with increasing score. Other variables which potentially may alter the gastrointestinal microbiota and secondarily DMF tolerance will be assessed, including the identification of subjects predisposed to functional bowel disorders via use of the Rome III functional bowel survey, a validated clinical tool to identify at-risk individuals, diet composition, antibiotic exposure, steroid treatments for neurological relapses, use of prebiotic , probiotic, or vitamin D supplements, and H2 blocker or proton pump inhibitor (PPI) therapy, as gut pH changes impact the gut flora composition.Additional data on mood change over 24 weeks of DMF therapy, using the Hamilton Anxiety Measurement (HAM) Rating Scale and Patient Health Questionnaire-9 (PHQ-9) Depression Scale, will be collected and correlated to DMF-emergent G.I. disturbances, and to changes in bacterial and archaeal species in the gut flora.

Conditions

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Multiple Sclerosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Dimethyl fumarate

Observation of impact of dimethyl fumarate treatment initiation on mood and gut microbiome over the first 6 months of therapy

Intervention Type DRUG

Other Intervention Names

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Tecfidera

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of a relapsing form of multiple sclerosis by McDonald criteria.
* Age 18 years or older.
* Able to provide informed consent.
* Treatment naïve to DMF, Fumaderm or other fumarate containing compound.
* Neurologically stable within 4 weeks prior to screening.
* Stable gross diet composition type (Western, vegetarian with dairy, vegan, gluten-limited, Paleo) within 12 weeks of screening visit.
* Able to complete study specific questionnaires and demographic information via HIPAA compliant secure internet based portal.
* No oral antibiotics within 4 weeks of screening.
* Able to abide by safety surveillance monitoring and management as part of standard of care.
* Able and willing to comply with the protocol requirements for the duration of the study.

Exclusion Criteria

* Treatment with immunosuppressive therapies (other than steroids) within 12 months of screening, experimental or FDA approved cell trafficking modulators, experimental immune cell vaccines, or stem cell therapy.
* G.I. diagnostic or therapeutic procedure within 24 weeks of screening visit, or at any time during participation in the study.
* Steroid therapy (oral or intravenous) within 4 weeks of screening visit.
* Chronic use of a proton pump inhibitor therapy (daily use for greater than 4 weeks) within 3 months of screening.
* Chronic use (i.e. daily use for greater than 4 weeks) of laxatives other than Colace within 6 months of screening.
* Intravenous antimicrobial therapy within 24 weeks of screening.
* Oral antimicrobial therapy within 4 weeks of screening.
* Dental procedure within 4 weeks of screening visit.
* Total parenteral nutrition (TPN) within 12 months of screening.
* History of Crohns disease, ulcerative colitis, biliary cirrhosis, celiac disease, chronic pancreatitis, gastric lap-band procedure, gastric or colon cancer, bowel resection, colitis within past 6 months.
* Women who are pregnant, breastfeeding, planning pregnancy, or potentially fertile and not willing to abide by effective contraception while being treated with DMF.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role collaborator

Virginia Simnad

OTHER

Sponsor Role lead

Responsible Party

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Virginia Simnad

MD, M.Sc

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Virginia I Simnad, MD

Role: PRINCIPAL_INVESTIGATOR

EvergreenHealth

Locations

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EvergreenHealth MS Center

Kirkland, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Shalom E Kilcup

Role: CONTACT

Phone: 425-899-5369

Email: [email protected]

Carey L Gonzales

Role: CONTACT

Phone: 425-899-5374

Email: [email protected]

Facility Contacts

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Shalom E Kilcup

Role: primary

Other Identifiers

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VIS2014

Identifier Type: -

Identifier Source: org_study_id