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

NCT05298670 | Unknown Phase 2

• 1 other identifier: MSMet
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effect of Metformin as add- on therapy for improving the outcome in RRMS patients.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Change in IL17 in both arms as measured by ELISA.

  Anti-inflammatory marker

  After 6 months

Secondary Outcomes (5)

• Percentage of Quality of Life deterioration in both arms measured by MSQOL-54.

  After 6 months

• Change in IL22 in both arms as measured by ELISA.

  After 6 months

• Malondialdehyde in both arms as measured by Colorimetric tests.

  After 6 months

• Degree of remyelination visualized by MRI, it depends on clinician's overview.

  After 6 months

• Degree of disability assessed by Expanded Disability Status Scale.

  After 6 months

Study Arms (2)

Metformin (Cidophage®) and Interferon Beta 1 a (Rebiff ® 44mcg or Avonex ®)

EXPERIMENTAL

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 ®).

Drug: MetFORMIN 1000 Mg Oral Tablet; Drug: Interferon beta-1a

Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)

ACTIVE COMPARATOR

Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®)

Drug: Interferon beta-1a

Interventions

MetFORMIN 1000 Mg Oral Tablet DRUG

Antidiabetic agent used to treat type 2 diabetes, and to prevent type 2 diabetes.

Also known as: Cidophage ®1000 mg tablets, CID, Giza, Egypt) tablet and Rebiff ® 44mcg or Avonex®

Metformin (Cidophage®) and Interferon Beta 1 a (Rebiff ® 44mcg or Avonex ®)

Interferon beta-1a DRUG

Disease Modifying Therapies (DMTs)

Also known as: Rebiff ® 44mcg or Avonex®

Interferon beta 1 a (Rebiff ® 44mcg or Avonex ®); Metformin (Cidophage®) and Interferon Beta 1 a (Rebiff ® 44mcg or Avonex ®)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• German University in Cairo: lead

Study Sites (1)

Nasser Institute for Research and Treatment

Cairo, Egypt

RECRUITING

Related Publications (19)

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  PMID: 22379455 BACKGROUND

• 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.

  PMID: 25200713 BACKGROUND

• 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.

  PMID: 33480077 BACKGROUND

• 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.

  PMID: 32454942 BACKGROUND

• 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.

  PMID: 26953870 BACKGROUND

• 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.

  PMID: 26680745 BACKGROUND

• 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.

  PMID: 32595595 BACKGROUND

• 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.

  PMID: 33161784 BACKGROUND

• 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.

  PMID: 31366635 BACKGROUND

• 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.

  PMID: 21470407 BACKGROUND

• 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.

  PMID: 32369446 BACKGROUND

• 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.

  PMID: 32719487 BACKGROUND

• 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.

  PMID: 34739637 BACKGROUND

• 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.

  PMID: 29931409 BACKGROUND

• 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.

  PMID: 31585093 BACKGROUND

• 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.

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• 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.

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• Abdelgaied MY, Rashad MH, El-Tayebi HM, Solayman MH. The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial. J Neurol. 2024 Mar;271(3):1124-1132. doi: 10.1007/s00415-023-12113-2. Epub 2023 Dec 9.

  PMID: 38070031 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Metformin; Tablets; Interferon beta-1a

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Mohamed Elsayed, master

CONTACT

+2001091282830; mohamed.yosefelsayed@student.guc.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research assistant in Clinical Pharmacology and Pharmacogenomics Research Gruop

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 28, 2022
• Study Start: February 1, 2022
• Primary Completion: February 28, 2023
• Study Completion: March 28, 2023
• Last Updated: March 20, 2023

Record last verified: 2023-03

Locations

EG (1)