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Rheumatoid ArthritisPhase 1/2NCT04068246

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

A Phase 1/2 study testing Metformin in people with Rheumatoid Arthritis, run by Sadat City University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
1 siteEgypt
Study dates
1 Aug 2019to 28 Feb 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Egypt1 site

  • Faculty of Pharmacy

    Shibīn al Kawm, Menoufia, 13829

Other trials in Egypt

About this study

Official title: The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Rheumatoid Arthritis Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial.

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.

Read the detailed description

Rheumatoid arthritis (RA) is a chronic, multisystem inflammatory disorder of unknown etiology. It is characterized by polyarthritis and systemic inflammation. The inflammation in the hyperplastic synovium can destruct the structure of affected joints. Although the exact molecular mechanism underlying the pathogenesis of RA remains unknown, it is suggested that T helper cell (Th) 17 plays a central role. Interleukin (IL)-17, mostly secreted by Th17, has synergistic effects with tumor necrosis factor- (TNF-α), IL-1β and IL-6 in cases of RA. 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 . In addition, metformin activated AMPK may inhibit mammalian target of rapamycin (mTOR), which then regulate the differentiation of T cells in vitro and in vivo. In particular, AMPK has been reported to be associated with the inhibition of TH17 cells through suppressing the phosphorylation of mTOR and its downstream signal transducers, suggesting the therapeutic potential of AMPK agonists. Besides the imbalance between Th17 cells and Treg cells is responsible for the chronic inflammation in RA, synovium hyperplasia also plays a central role in the joint destruction. It has been reported that rapamycin, an inhibitor of mTOR, is able to significantly reduce fibroblastlike synovial cell invasion in RA via suppressing mTOR signaling pathway. 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.

Being tested
Metformin, Placebo
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

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

  • PlaceboDrug

    Placebo tablet plus plus Methotrexate 7.5 mg weekly

Study groups in NCT04068246
Study groupRoleWhat they receive
Control groupPlacebo comparatorpatients will receive the standard therapy (methotrexate) plus placebo tablets
Receives: Drug: Placebo
Metformin groupExperimentalpatients will receive the standard therapy plus 1 g metformin daily.
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: week 12

  2. 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

    Measured: week 12

  3. 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).

    Measured: week 12

Secondary outcomes (9)

  1. the Short Form 36 (SF-36) Health Survey

    both the physical component score [PCS] and the mental component score [MCS])

    Measured: week 12

  2. HAQ-DI (Health Assessment Score- Disability index)

    HAQ-DI (Health Assessment Score- Disability index), in which patients are asked to rate their capacity to perform 20 activities of daily living (ADL). Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section

    Measured: week 12

  3. AMPK expression

    AMPK expression in synovium or serum

    Measured: at baseline and at week 12

  4. IGF-IR expression

    IGF-IR expression in Blood

    Measured: at baseline and at week 12

  5. TNF-α

    Serum level Tumor necrosis factor- alpha (TNF-α)

    Measured: at baseline and at week 12

  6. TGF-Beta1

    Serum level tissue growth factor beta 1

    Measured: at baseline and at week 12

  7. Inteleukins

    Serum levels of Interleukins (IL) IL-17, IL-1β , IL-6 \& IL-10

    Measured: at baseline and at week 12

  8. CRP

    Serum level of C-reactive protein (CRP)

    Measured: at baseline and at week 12

  9. Drug Adverse effects

    Adverse effect incidence: adverse effect will be reported by patients or their caregivers and recorded by investigator.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2019
  2. Study start1 Aug 2019
  3. Primary completion31 Dec 2020
  4. Study completion28 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04068246
Sponsor's protocol ID
PMRR-8-2019
Status last verified
Jul 2025
First submitted
21 Aug 2019
Last updated
14 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • 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.

    PubMed 33773207

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Metformin in people with Rheumatoid Arthritis, run by Sadat City University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ACR 20% improvement criteria (ACR20) response rate (time frame: week 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04068246, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.

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