IIT9: Pilot Study to Assess Dimethyl Fumarate Related GI Symptom Mitigation

• Sponsor: Rocky Mountain MS Research Group, LLC (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02217982
• Collaborator: Biogen (Industry)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Remitting Multiple Sclerosis	Drug: Simethicone; Drug: Loperamide; Other: Peanut Butter	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Assess Dimethyl Fumarate (Tecfidera) Related GI Symptom Mitigation Via Food Bolus Alteration and Simethicone/Loperamide Administration
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Reported GI Symptoms [7 Weeks]

   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.

Secondary Outcome Measures

1. Diarrhea Reduction [7 Weeks]

   The secondary objective is to assess the reduction in diarrhea in the treatment group compared to the control.

Other Outcome Measures

1. Number of Participants With Pre-Existing GI Conditions [7 Weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain MS Research Group	Salt Lake City	Utah	United States	84103

Sponsors and Collaborators

• Rocky Mountain MS Research Group, LLC
• Biogen

Investigators

• Principal Investigator: John F Foley, MD, Rocky Mountain MS Research Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John F. Foley, MD, PI, Rocky Mountain MS Research Group, LLC
• ClinicalTrials.gov Identifier: NCT02217982
• Other Study ID Numbers: 009-001-TEC
• First Posted: Aug 15, 2014
• Last Update Posted: Mar 23, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Simethicone; Loperamide; Antidiarrheals

Study Results

Participant Flow

Arm/Group Title	Control Group	Treatment Arm
Arm/Group Description	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.	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. Simethicone Loperamide Peanut Butter
Period Title: Overall Study
STARTED	1	4
COMPLETED	0	3
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Control Group	Treatment Arm	Total
Arm/Group Description	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.	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. Simethicone Loperamide Peanut Butter	Total of all reporting groups
Overall Participants	1	4	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	4 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%	4 100%	5 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	1 100%	4 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Reported GI Symptoms
Description	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.
Time Frame	7 Weeks

Outcome Measure Data

Analysis Population Description

Trial was shut down early as not enough patients qualified with GI symptoms their first 2 weeks after initiating DMF therapy

Arm/Group Title	Control Group	Treatment Arm
Arm/Group Description	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.	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. Simethicone Loperamide Peanut Butter
Measure Participants	0	0
	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Not enough patients qualified and the study was terminated early.

Arm/Group Title	Control Group	Treatment Arm
Arm/Group Description	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.	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. Simethicone Loperamide Peanut Butter
Measure Participants	0	0
	0	0

3. Other Pre-specified Outcome

Title	Number of Participants With Pre-Existing GI Conditions
Description	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.
Time Frame	7 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	approximately 10 weeks from consent to end of study
Arm/Group Title	Control Group		Treatment Arm
Arm/Group Description	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.		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. Simethicone Loperamide Peanut Butter
All Cause Mortality
	Control Group		Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control Group		Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Control Group		Treatment Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/4 (0%)

Limitations/Caveats

This trial was closed down early because the anticipated number of patients experiencing GI symptoms was not met - therefore not enough patients qualified for the treatment and control arms for analysis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.