Gastrointestinal Tolerability of Diroximel Fumarate Compared with Dimethyl Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: Clinical Trial Study
The primary objective of this study is to compare the gastrointestinal tolerability of diroximel fumarate versus dimethyl fumarate in patients with relapsing–remitting multiple sclerosis during a 5-week treatment period
Design
This study is a randomized, two-arm, parallel-group, open-label phase 2 clinical trial conducted on 100 patients with relapsing–remitting multiple sclerosis. Randomization was performed in a 1:1 ratio using the RAND function in Microsoft Excel. The sample size was calculated based on the comparison of gastrointestinal adverse event incidence between the two groups, with a significance level of 0.10 and 70% power
Settings and conduct
This is a randomized, prospective clinical trial conducted at Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences. Eligible RRMS patients are randomized into two groups and receive oral medications for 5 weeks. The study is open-label with no blinding.
Participants/Inclusion and exclusion criteria
Patients with relapsing–remitting multiple sclerosis (RRMS)
Age between 18 and 65 years
Diagnosis of RRMS based on McDonald criteria
Ability to take oral medications
Not pregnant or breastfeeding
Signed informed consen
Intervention groups
Group 1: Diroximel fumarate (DRF)
Dose: 231 mg twice daily in the first week
Dose: 462 mg twice daily from week 2 to week 5
Group 2: Dimethyl fumarate (DMF)
Dose: 120 mg twice daily in the first week
Dose: 240 mg twice daily from week 2 to week 5
Main outcome variables
Gastrointestinal tolerability; severity of nausea; frequency of vomiting; upper abdominal pain; lower abdominal pain; diarrhea; impact of gastrointestinal symptoms on daily activities; incidence of at least one gastrointestinal adverse event
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20260202068737N1
Registration date:2026-02-05, 1404/11/16
Registration timing:prospective
Last update:2026-02-05, 1404/11/16
Update count:0
Registration date
2026-02-05, 1404/11/16
Registrant information
Name
Roya Bahram pourian
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 61 3311 1565
Email address
bahrampourian.roya67@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2026-03-20, 1404/12/29
Expected recruitment end date
2026-04-23, 1405/02/03
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Gastrointestinal Tolerability of Diroximel Fumarate Compared with Dimethyl Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: Clinical Trial Study
Public title
A Clinical Trial Comparing Gastrointestinal Tolerability of Diroximel Fumarate and Dimethyl Fumarate in Patients with RRMS
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
A confirmed diagnosis of relapsing–remitting multiple sclerosis (RRMS) according to the McDonald criteria
Age between 18 and 65 years at the time of study entry.
Not pregnant or breastfeeding at screening, with agreement to use effective contraception during the study period
No history of hypersensitivity or severe adverse reactions to fumarates or related compounds.
No active or clinically significant gastrointestinal disease that could interfere with drug tolerability assessment
No active or clinically significant gastrointestinal disease that could interfere with drug tolerability assessment
No severe hepatic or renal impairment based on medical history, physical examination, and baseline laboratory evaluations.
Acceptable baseline laboratory values, including hematologic and biochemical parameters.
No diagnosis of progressive forms of multiple sclerosis.
No prior treatment with dimethyl fumarate or switching from DMF to DRF before screening.
Willingness and ability to complete daily study questionnaires throughout the follow-up period.
Provision of written informed consent prior to enrollment and randomization.
Exclusion criteria:
Age
From 18 years old to 65 years old
Gender
Both
Phase
4
Groups that have been masked
No information
Sample size
Target sample size:
40
Randomization (investigator's opinion)
Randomized
Randomization description
After confirming eligibility criteria and obtaining written informed consent, eligible patients will be randomly assigned in a 1:1 allocation ratio to receive either diroximel fumarate (DRF) or dimethyl fumarate (DMF). Randomization will be performed by a statistician using a random number table or validated statistical software (such as SPSS or R). To minimize selection bias and ensure balance of baseline characteristics between the two treatment groups, treatment allocation will be conducted in an unpredictable manner. Given the open-label design of the study, both investigators and participants will be aware of the assigned treatment
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of the University
Street address
Block 4 (Unit Golestan 4), Golestan Hospital, Golestan Street, Golestan Town, Ahvaz, Khuzestan Province, Iran Ahvaz Jundishapur University of Medical Sciences
City
Ahvaz
Province
Khouzestan
Postal code
6115613811
Approval date
2026-01-30, 1404/11/10
Ethics committee reference number
IR.AJUMS.REC.1404.584
Health conditions studied
1
Description of health condition studied
Relapsing–Remitting Multiple Sclerosis (RRMS)
ICD-10 code
G35
ICD-10 code description
Multiple sclerosis
Primary outcomes
1
Description
Drug gastrointestinal tolerability, measured by IGISIS and GGISIS scales. This variable includes assessment of the occurrence, severity, duration, and functional impact of key gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea during the 5-week treatment period
Timepoint
Measurements and assessments will be conducted daily from the first day of treatment (week 1) through the end of week 5 (day 35). Additionally, safety follow-ups and adverse event monitoring will continue for two weeks after the treatment period.
Method of measurement
The primary outcome, gastrointestinal tolerability, is measured using two validated questionnaires: IGISIS (Individual Gastrointestinal Symptom and Impact Scale) and GGISIS (Global Gastrointestinal Symptom and Impact Scale). Patients report the severity of gastrointestinal symptoms—including nausea, vomiting, upper and lower abdominal pain, and diarrhea—daily on a numerical scale from 0 to 10. Additionally, the duration of symptoms and their impact on daily activities are recorded. These questionnaires are completed daily, and the data are collected for statistical analysis
Secondary outcomes
1
Description
Treatment adherence: The extent of continued drug use and the number of doses taken during the 5-week period
Timepoint
Measurements and assessments will be conducted daily from the first day of treatment (week 1) through the end of week 5 (day 35). Additionally, safety follow-ups and adverse event monitoring will continue for two weeks after the treatment period
Method of measurement
The primary outcome, gastrointestinal tolerability, is measured using two validated questionnaires: IGISIS (Individual Gastrointestinal Symptom and Impact Scale) and GGISIS (Global Gastrointestinal Symptom and Impact Scale). Patients report the severity of gastrointestinal symptoms—including nausea, vomiting, upper and lower abdominal pain, and diarrhea—daily on a numerical scale from 0 to 10. Additionally, the duration of symptoms and their impact on daily activities are recorded. These questionnaires are completed daily, and the data are collected for statistical analysis
2
Description
Health-related quality of life (HRQoL): Assessed by the SF-36 questionnaire at baseline and at the end of treatment, including physical (PCS) and mental (MCS) component summaries
Timepoint
Measurements and assessments will be conducted daily from the first day of treatment (week 1) through the end of week 5 (day 35). Additionally, safety follow-ups and adverse event monitoring will continue for two weeks after the treatment period
Method of measurement
Health-related quality of life (HRQoL) is assessed using the standardized SF-36 questionnaire at baseline and at the end of the treatment period. The questionnaire covers 8 domains, with scores ranging from 0 to 100 for each domain. Two main summary components, Physical Component Summary (PCS) and Mental Component Summary (MCS), are derived from the questionnaire. Higher scores indicate better quality of life
Intervention groups
1
Description
Intervention group: The first group receives diroximel fumarate (DRF) with a dose of 231 mg twice daily during the first week, and 462 mg twice daily from week 2 to week 5
Category
Treatment - Drugs
2
Description
Intervention group: The second group receives dimethyl fumarate (DMF) with a dose of 120 mg twice daily during the first week, and 240 mg twice daily from week 2 to week 5
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences
Central Building, Pasdaran Street, Ahvaz, Khuzestan Province, Iran Research and Technology Deputy Office, Ahvaz Jundishapur University of Medical Sciences
City
Ahvaz
Province
Khouzestan
Postal code
۶۱۱۳۵۱۳۱۱۱
Phone
+98 61 3334 0000
Email
rafiei-a@ajums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Ahvaz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Roya Bahram pourian
Position
Resident
Latest degree
Specialist
Other areas of specialty/work
Neuroscience
Street address
Ahvaz, Ostadan Quay, West Coast Boulevard, Golestan Boulevard
City
Ahvaz
Province
Khouzestan
Postal code
۶۱۱۳۵۱۳۱۱۱
Phone
+98 61 3311 1565
Fax
Email
bahrampourian.roya67@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Roya Bahram pourian
Position
Resident
Latest degree
Specialist
Other areas of specialty/work
Neuroscience
Street address
Ahvaz, Ostadan Quay, West Coast Boulevard, Golestan Boulevard
City
Ahvaz
Province
Khouzestan
Postal code
۶۱۱۳۵۱۳۱۱۱
Phone
+98 61 3311 1565
Fax
Email
bahrampourian.roya67@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Roya Bahram pourian
Position
Resident
Latest degree
Specialist
Other areas of specialty/work
Neuroscience
Street address
Ahvaz, Ostadan Quay, West Coast Boulevard, Golestan Boulevard
City
Ahvaz
Province
Khouzestan
Postal code
۶۱۱۳۵۱۳۱۱۱
Phone
+98 61 3311 1565
Fax
Email
bahrampourian.roya67@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available