The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Rheumatoid Arthritis Patients

NCT04068246 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PMRR-8-2019
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Metformin, a traditional antidiabetic medication, exerts glucose lowering effects by activating AMP-activated protein kinase (AMPK), a critical enzyme involved in the lipid and glucose metabolism. In addition to the antidiabetic effect, metformin has been shown to inhibit Lipopolysaccharide-Induced Inflammation (LPS)-induced inflammation by suppress NF-κB production, which is also regulated by AMPK. These regulatory effects of AMPK on the inflammation, immune and fibroblast-like synovial cells have prompted the investigation on the effects of metformin on rheumatoid arthritis.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• ACR 20% improvement criteria (ACR20) response rate

  based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level

  week 12

• ACR50 & ACR70 response rate

  based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level

  week 12

• Disease activity scale in 28 joints (DAS-28)

  Scale assessing severity of rheumatoid arthritis based on number of tender, swollen joints, erythrocyte sedimentation rate (ESR) levels, and patient self-assessment of his condition (global health assessment). Whereas "28" describes the number of different joints including in the measurement: proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2), knees (2).

  week 12

Secondary Outcomes (9)

• the Short Form 36 (SF-36) Health Survey

  week 12

• HAQ-DI (Health Assessment Score- Disability index)

  week 12

• AMPK expression

  at baseline and at week 12

• IGF-IR expression

  at baseline and at week 12

• TNF-α

  at baseline and at week 12

Study Arms (2)

Control group

PLACEBO COMPARATOR

patients will receive the standard therapy (methotrexate) plus placebo tablets

Drug: Placebo

Metformin group

EXPERIMENTAL

patients will receive the standard therapy plus 1 g metformin daily.

Drug: Metformin

Interventions

Metformin DRUG

1000 mg of Metformin table taken orally daily plus Methotrexate 7.5 mg weekly

Metformin group

Placebo DRUG

Placebo tablet plus plus Methotrexate 7.5 mg weekly

Control group

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with active rheumatoid arthritis based on DAS28 score. Patients received the standard therapy (i.e. one or more conventional DMARDs) for at least three months.

You may not qualify if:

• Known hypersensitivity to metformin.
• Patients who have a prior diagnosis with diabetes mellitus.
• Patients receive metformin for any other indications.
• Patients with congestive heart failure.
• Patients with a history of myocardial infarction.
• Patients with severe anemia.
• Patients with active infections or other inflammatory diseases.
• Patients receiving biological therapy.
• Pregnancy or lactation.
• Patients with impaired liver functions.
• Patients with impaired kidney functions (serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL in males and females respectively).
• Patients with malignancies.

Sponsors & Collaborators

• Sadat City University: lead

Study Sites (1)

Faculty of Pharmacy

Shibīn al Kawm, Menoufia, 13829, Egypt

Location

Related Publications (1)

• 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.

  PMID: 33773207 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Metformin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy, PhD.

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 28, 2019
• Study Start: August 1, 2019
• Primary Completion: December 31, 2020
• Study Completion: February 28, 2021
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

EG (1)