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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
German University in Cairo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

First Posted
March 17, 2022
Last Updated
March 17, 2023
Sponsor
German University in Cairo
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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:
PubMed Identifier
22379455
Citation
Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol. 2011 Sep;9(3):409-16. doi: 10.2174/157015911796557911.
Results Reference
background
PubMed Identifier
25200713
Citation
Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, Thompson AJ. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology. 2014 Sep 9;83(11):1022-4. doi: 10.1212/WNL.0000000000000768. No abstract available.
Results Reference
background
PubMed Identifier
33480077
Citation
Sormani MP, De Rossi N, Schiavetti I, Carmisciano L, Cordioli C, Moiola L, Radaelli M, Immovilli P, Capobianco M, Trojano M, Zaratin P, Tedeschi G, Comi G, Battaglia MA, Patti F, Salvetti M; Musc-19 Study Group. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis. Ann Neurol. 2021 Apr;89(4):780-789. doi: 10.1002/ana.26028. Epub 2021 Feb 9.
Results Reference
background
PubMed Identifier
32454942
Citation
Pegoretti V, Swanson KA, Bethea JR, Probert L, Eisel ULM, Fischer R. Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development. Oxid Med Cell Longev. 2020 May 12;2020:7191080. doi: 10.1155/2020/7191080. eCollection 2020.
Results Reference
background
PubMed Identifier
26953870
Citation
Negrotto L, Farez MF, Correale J. Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis. JAMA Neurol. 2016 May 1;73(5):520-8. doi: 10.1001/jamaneurol.2015.4807.
Results Reference
background
PubMed Identifier
26680745
Citation
Triggle CR, Ding H. Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium. Acta Physiol (Oxf). 2017 Jan;219(1):138-151. doi: 10.1111/apha.12644. Epub 2016 Jan 13.
Results Reference
background
PubMed Identifier
32595595
Citation
Sportelli C, Urso D, Jenner P, Chaudhuri KR. Metformin as a Potential Neuroprotective Agent in Prodromal Parkinson's Disease-Viewpoint. Front Neurol. 2020 Jun 12;11:556. doi: 10.3389/fneur.2020.00556. eCollection 2020.
Results Reference
background
PubMed Identifier
33161784
Citation
Demare S, Kothari A, Calcutt NA, Fernyhough P. Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system. Expert Rev Neurother. 2021 Jan;21(1):45-63. doi: 10.1080/14737175.2021.1847645. Epub 2020 Dec 4.
Results Reference
background
PubMed Identifier
31366635
Citation
Shi Q, Liu S, Fonseca VA, Thethi TK, Shi L. Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus. BMJ Open. 2019 Jul 30;9(7):e024954. doi: 10.1136/bmjopen-2018-024954.
Results Reference
background
PubMed Identifier
21470407
Citation
Dowling RJ, Goodwin PJ, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Med. 2011 Apr 6;9:33. doi: 10.1186/1741-7015-9-33.
Results Reference
background
PubMed Identifier
32369446
Citation
Brown JR, Chan DK, Shank JJ, Griffith KA, Fan H, Szulawski R, Yang K, Reynolds RK, Johnston C, McLean K, Uppal S, Liu JR, Cabrera L, Taylor SE, Orr BC, Modugno F, Mehta P, Bregenzer M, Mehta G, Shen H, Coffman LG, Buckanovich RJ. Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer. JCI Insight. 2020 Jun 4;5(11):e133247. doi: 10.1172/jci.insight.133247.
Results Reference
background
PubMed Identifier
32719487
Citation
Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.
Results Reference
background
PubMed Identifier
34739637
Citation
El-Khayat SM, Abouegylah M, Abdallah D, Geweil AG, Elenbaby AM, Zahra OS. The effect of metformin when combined with neoadjuvant chemotherapy in breast cancer patients. Med Oncol. 2021 Nov 5;39(1):1. doi: 10.1007/s12032-021-01599-3.
Results Reference
background
PubMed Identifier
29931409
Citation
El-Fatatry BM, Ibrahim OM, Hussien FZ, Mostafa TM. Role of metformin in oxaliplatin-induced peripheral neuropathy in patients with stage III colorectal cancer: randomized, controlled study. Int J Colorectal Dis. 2018 Dec;33(12):1675-1683. doi: 10.1007/s00384-018-3104-9. Epub 2018 Jun 21.
Results Reference
background
PubMed Identifier
31585093
Citation
Neumann B, Baror R, Zhao C, Segel M, Dietmann S, Rawji KS, Foerster S, McClain CR, Chalut K, van Wijngaarden P, Franklin RJM. Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells. Cell Stem Cell. 2019 Oct 3;25(4):473-485.e8. doi: 10.1016/j.stem.2019.08.015.
Results Reference
background
PubMed Identifier
31620963
Citation
Houshmand F, Barati M, Golab F, Ramezani-Sefidar S, Tanbakooie S, Tabatabaei M, Amiri M, Sanadgol N. Metformin-induced AMPK activation stimulates remyelination through induction of neurotrophic factors, downregulation of NogoA and recruitment of Olig2+ precursor cells in the cuprizone murine model of multiple sclerosis. Daru. 2019 Dec;27(2):583-592. doi: 10.1007/s40199-019-00286-z. Epub 2019 Oct 16.
Results Reference
background
PubMed Identifier
7613530
Citation
Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995 Jun;4(3):187-206. doi: 10.1007/BF02260859.
Results Reference
background
PubMed Identifier
33773207
Citation
Abdallah MS, Alarfaj SJ, Saif DS, El-Naggar ME, Elsokary MA, Elsawah HK, Abdelsattar Zaki S, Wahsh EA, Abo Mansour HE, Mosalam EM. The AMPK modulator metformin as adjunct to methotrexate in patients with rheumatoid arthritis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. Int Immunopharmacol. 2021 Jun;95:107575. doi: 10.1016/j.intimp.2021.107575. Epub 2021 Mar 24.
Results Reference
background

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Drug Repurposing Using Metformin for Improving the Therapeutic Outcome in Multiple Sclerosis Patients

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