Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
Primary Purpose
Multiple Sclerosis
Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
MetFORMIN 1000 Mg Oral Tablet
Interferon beta-1a
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Age between 18 and 50 years at time of signing informed consent form.
- Relapsing- remitting multiple sclerosis as per the McDonald 2017 criteria, including an MRI brain satisfying the 2017 radiological criteria.
- Full-field visual evoked potential (VEP) P100 latency in at least one eye of ≥118 ms.
- Kurtzke EDSS step 0.0 - 6.0.
- At the time of screening, being treated with a stable dose for at least 6 months of a category 1 multiple sclerosis DMT or for at least 2 years with a category 2 DMT.
Exclusion Criteria:
- People taking medication for Diabetes Mellitus at screening.
- Female participants who are pregnant, lactating, planning pregnancy, or unwilling to use reliable contraception during the trial.
- Significant liver impairment; alanine aminotransferase > 3 times the upper limit of normal.
- People suffering from congestive heart failure, chronic lung disease with hypoxia, and severe anemia.
- Patients with compromised renal function ((eGFR <60 mL/min/1.73m2) or coexistent hypoxic conditions should not be given metformin.
- Chronic or acute intake of large amounts of alcohol may potentiate the effect of metformin on lactate metabolism.
- Patients had been prescribed oral, intravenous, and intramuscular corticosteroids for one month prior to study.
Sites / Locations
- Nasser Institute for Research and TreatmentRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Metformin (Cidophage®) and Interferon Beta 1 a (Rebiff ® 44mcg or Avonex ®)
Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)
Arm Description
Metformin 1000 mg (Cidophage® 1000 mg tablets, CID, Giza, Egypt) tablet twice daily for 6 months as add on therapy with Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®).
Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)
Outcomes
Primary Outcome Measures
Change in IL17 in both arms as measured by ELISA.
Anti-inflammatory marker
Secondary Outcome Measures
Percentage of Quality of Life deterioration in both arms measured by MSQOL-54.
Assessment of quality of life for patients, The highest and lowest values refer to the satisfaction degree of patients
Change in IL22 in both arms as measured by ELISA.
Anti-inflammatory marker
Malondialdehyde in both arms as measured by Colorimetric tests.
Anti-oxidant marker
Degree of remyelination visualized by MRI, it depends on clinician's overview.
Determination of T2 lesions
Degree of disability assessed by Expanded Disability Status Scale.
Determination disability level (0 - 6), The lowest value means that it is best outcome and the highest value is the worst outcome.
Full Information
NCT ID
NCT05298670
First Posted
March 17, 2022
Last Updated
March 17, 2023
Sponsor
German University in Cairo
1. Study Identification
Unique Protocol Identification Number
NCT05298670
Brief Title
Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
Official Title
Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2022 (Actual)
Primary Completion Date
February 28, 2023 (Actual)
Study Completion Date
March 28, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
German University in Cairo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study aims to evaluate the effect of Metformin as add- on therapy for improving the outcome in RRMS patients.
Detailed Description
Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. Worldwide, there are about 2.3 million MS patients. Women are twice as likely to have MS as men. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life.
The four main types of multiple sclerosis are clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). This research focuses on RRMS as it is the most common type (80%- 85%).
Elevated level of Interleukins, and oxidative stress parameters are associated with MS pathology which exaggerated the myelin destruction, axonal degradation, and inflammatory cascade.
Metformin has a global safety record, is well-tolerated by the majority of patients and is used by roughly 125 million people worldwide, so a lot of studies inside and outside Egypt investigates their potential effect in different disorders as neurodegenerative diseases and cancer. Despite the prevalence of animal studies which explored Metformin neuroprotective effects by decreasing T- helper cells (Th 1 and Th 17) and improving Oligodendrocyte progenitor cell responsiveness to induce remyelination, clinical trials are still insufficient which motivate us to investigate the promising effect of Metformin as add-on treatment in RRMS patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin (Cidophage®) and Interferon Beta 1 a (Rebiff ® 44mcg or Avonex ®)
Arm Type
Experimental
Arm Description
Metformin 1000 mg (Cidophage® 1000 mg tablets, CID, Giza, Egypt) tablet twice daily for 6 months as add on therapy with Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®).
Arm Title
Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)
Arm Type
Active Comparator
Arm Description
Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)
Intervention Type
Drug
Intervention Name(s)
MetFORMIN 1000 Mg Oral Tablet
Other Intervention Name(s)
Cidophage ®1000 mg tablets, CID, Giza, Egypt) tablet and Rebiff ® 44mcg or Avonex®
Intervention Description
Antidiabetic agent used to treat type 2 diabetes, and to prevent type 2 diabetes.
Intervention Type
Drug
Intervention Name(s)
Interferon beta-1a
Other Intervention Name(s)
Rebiff ® 44mcg or Avonex®
Intervention Description
Disease Modifying Therapies (DMTs)
Primary Outcome Measure Information:
Title
Change in IL17 in both arms as measured by ELISA.
Description
Anti-inflammatory marker
Time Frame
After 6 months
Secondary Outcome Measure Information:
Title
Percentage of Quality of Life deterioration in both arms measured by MSQOL-54.
Description
Assessment of quality of life for patients, The highest and lowest values refer to the satisfaction degree of patients
Time Frame
After 6 months
Title
Change in IL22 in both arms as measured by ELISA.
Description
Anti-inflammatory marker
Time Frame
After 6 months
Title
Malondialdehyde in both arms as measured by Colorimetric tests.
Description
Anti-oxidant marker
Time Frame
After 6 months
Title
Degree of remyelination visualized by MRI, it depends on clinician's overview.
Description
Determination of T2 lesions
Time Frame
After 6 months
Title
Degree of disability assessed by Expanded Disability Status Scale.
Description
Determination disability level (0 - 6), The lowest value means that it is best outcome and the highest value is the worst outcome.
Time Frame
After 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 18 and 50 years at time of signing informed consent form.
Relapsing- remitting multiple sclerosis as per the McDonald 2017 criteria, including an MRI brain satisfying the 2017 radiological criteria.
Full-field visual evoked potential (VEP) P100 latency in at least one eye of ≥118 ms.
Kurtzke EDSS step 0.0 - 6.0.
At the time of screening, being treated with a stable dose for at least 6 months of a category 1 multiple sclerosis DMT or for at least 2 years with a category 2 DMT.
Exclusion Criteria:
People taking medication for Diabetes Mellitus at screening.
Female participants who are pregnant, lactating, planning pregnancy, or unwilling to use reliable contraception during the trial.
Significant liver impairment; alanine aminotransferase > 3 times the upper limit of normal.
People suffering from congestive heart failure, chronic lung disease with hypoxia, and severe anemia.
Patients with compromised renal function ((eGFR <60 mL/min/1.73m2) or coexistent hypoxic conditions should not be given metformin.
Chronic or acute intake of large amounts of alcohol may potentiate the effect of metformin on lactate metabolism.
Patients had been prescribed oral, intravenous, and intramuscular corticosteroids for one month prior to study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mohamed Elsayed, master
Phone
+2001091282830
Email
mohamed.yosefelsayed@student.guc.edu.eg
Facility Information:
Facility Name
Nasser Institute for Research and Treatment
City
Cairo
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamed Hamed, PhD
12. IPD Sharing Statement
Citations:
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Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients
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