Pilot Study to Assess Dimethyl Fumarate Related GI Symptom Mitigation (IIT9)

A Pilot Study to Assess Dimethyl Fumarate (Tecfidera) Related GI Symptom Mitigation Via Food Bolus Alteration and Simethicone/Loperamide Administration

Single site, open label, randomized design in patients with relapsing forms of Multiple Sclerosis. At the Screening Visit, the patient will be given a diary containing the MAGIS scale to be completed once a day for the first two weeks while on Dimethyl Fumarate (DMF), including the titration period.

After two weeks or if a patient experiences 3 or more consecutive days of GI symptoms in any category of ≥3.5, the patient will return for a Baseline Visit. The MAGIS diary will be reviewed by the coordinator. Any patient who has reported an average MAGIS score of greater than or equal to 3.5 in at least one of the key categories will be randomized to a standard therapy or treatment arm. Patients who report a MAGIS of less than 3.5 during this period will be terminated from the study at this visit. Patients with an average reported MAGIS of greater than 6.5 at Baseline will be placed in the treatment arm.

Patients who are randomized to the treatment arm will be instructed to take 125 mg simethicone and one tablespoon of a high fat food (peanut butter) 10 minutes prior to each DMF dose. If the average MAGIS score is greater than 3.5 in the diarrhea category they will also be instructed to take 2 mg loperamide three times daily.

Patients randomized to the standard therapy arm will be instructed to follow the normal dosing regimen for DMF with a food bolus of their choice prior to dosing. If severe symptoms (MAGIS >6.5) are noted at any time post randomization in any MAGIS category, crossover to the treatment arm will be allowed. Both groups will be asked to rate their GI symptoms over the past 24 hours using the MAGIS scale once daily.

Both treatment arms will be observed for 6 weeks. MAGIS will be recorded once daily. Patients will return to the clinic at Week 3 and Week 6/End of Treatment for diary and compliance review. After Week 6, patients will be instructed to return to a standard therapy. MAGIS will be recorded for one more week and collected at Week 7/End of Study.

Study Overview

• Status: Terminated
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Simethicone; Drug: Loperamide; Other: Peanut Butter

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Rocky Mountain MS Research Group

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:

1. Decision to treat with DMF must precede enrollment
2. Ability to understand the purpose and risk of the study and provide authorization for the use of protected health information in accordance with the monitoring agency
3. Men or women 18 years of age or older at the time of informed consent
4. Naïve to DMF or fumaric acid esters
5. Confirmed diagnosis of a relapsing form of multiple sclerosis as verified by the Principal Investigator

Exclusion Criteria:

1. Unable to unwilling to comply with study requirements as outlined in the informed consent
2. Known active malignancies or any other major comorbidities that, in the opinion of the Investigator, would affect the outcome of the study
3. Pregnant or breastfeeding or likely to become pregnant during the course of the study. Women of child-bearing potential must practice an acceptable form of birth control
4. Previous treatment with dimethyl fumarate
5. Past history of GI malignancy, gastric ulceration refractory to medical resolution, history of gastrectomy. At the discretion of the PI, resolved GI ulceration, gastroesophageal reflux will not be exclusionary
6. Known sensitivity or allergic reaction to peanuts, simethicone, or loperamide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Patients randomized to the standard therapy arm will be instructed to follow the normal dosing regimen for DMF with a food bolus of their choice prior to dosing. If severe symptoms (MAGIS >6.5) are noted at any time post randomization in any MAGIS category, crossover to the treatment arm will be allowed. Both groups will be asked to rate their GI symptoms over the past 24 hours using the MAGIS scale once daily.
Active Comparator: Treatment Arm; Patients who are randomized to the treatment arm will be instructed to take 125 mg simethicone and one tablespoon of a high fat food (peanut butter)10 minutes prior to each DMF dose. If the average MAGIS score is greater than 3.5 in the diarrhea category they will also be instructed to take 2 mg loperamide three times daily.	Drug: Simethicone; Other Names: Gas-X; Drug: Loperamide; Other Names: Imodium; Other: Peanut Butter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reported GI Symptoms	The primary endpoint will be severity of GI events as measured by the MAGIS scale for subjects in the treatment arm compared to the standard therapy arm.	7 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diarrhea Reduction	The secondary objective is to assess the reduction in diarrhea in the treatment group compared to the control.	7 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Pre-Existing GI Conditions	The tertiary objective is to gather further data regarding pre-existing conditions (GE reflex, gastric bypass, stomach ulcer, etc) and their possible relationship to GI symptoms when initiating DMF.	7 Weeks

Collaborators and Investigators

• Sponsor: Rocky Mountain MS Research Group, LLC
• Collaborators: Biogen

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: August 13, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Dermatologic Agents; Antifoaming Agents; Emollients; Simethicone; Loperamide; Antidiarrheals
• Other Study ID Numbers: 009-001-TEC