The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Patients With Knee Osteoarthritis

NCT04767841 | Withdrawn Phase 1 DMC

• 1 other identifier: 10/2021RHU
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

metformin alleviates drug-induced osteoarthritis (OA)-like change in mice knee joint through activating autophagy and downregulating apoptosis. Metformin exerts its protective effects against OA through the AMPKa2/ SIRT1 pathway. Metformin suppresses IL-1β-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin's potential in prevention and treatment of osteoarthritic joint disease.

Conditions

Osteo Arthritis Knee

Outcome Measures

Primary Outcomes (1)

• Visual Analogue scale assessment of pain

  the change of Visual Analogue Scale (VAS) pain score from baseline to posttreatment

  week 12

Secondary Outcomes (7)

• WOMAC change

  week 12

• the change of Short Form 36 Questionnaire (SF-36) score from baseline to posttreatment

  week 12

• Adverse drug reaction

  12 weeks

• AMPK expression

  12 weeks

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

  12 weeks

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 1000 mg daily plus Celecoxib 200mg capsule

Drug: Metformin

Placebo

EXPERIMENTAL

Placebo tablet daily plus Celecoxib 200mg capsule

Drug: Placebo

Interventions

Metformin DRUG

Metformin 1000mg tablet plus celecoxib 200 mg capsule

Metformin

Placebo DRUG

Placebo tablet plus celecoxib 200 mg capsule

Placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Primary osteoarthritis Patients recruited were between 30 to 60 years of age, with X-ray confirmed Kellgren-Lawrence grade13 II or III severity primary tibiofemoral OA, according to the American College of Rheumatology criteria.

You may not qualify if:

• Those patients were excluded from the present study who:
• were of age less than 30 years or more than 60 years
• presented with active concomitant gastroduodenal disorders, hepatic and renal impairment within last 30 days prior to receiving the study drug
• were diagnosed to have any inflammatory arthritis, gout or acute trauma of the knee, hip or spine; accompanying OA of the hip of sufficient severity to interfere with the functional assessment of the knee
• had previous or ongoing treatment with oral SYSDOA (e.g., glucosamine sulphate, chondroitin sulphate, diacerein, piascledine), anti-depressants, tranquillisers, antacids or antibiotics; were having active cardiac lesion or hypertension, were pregnant females and those who were planning their pregnancy during the study
• were having a known hypersensitivity to the used medications
• have persistent diarrhoea or laxative use; severe gastrointestinal disorders, severe obesity, severe parenchymal organ disease, or anaemia (haemoglobin\< 10.0 g/ dl or haematocrit \< 30%).
• Patients who received oral, intramuscular, intraarticular or soft tissue injections of corticosteroids within last eight weeks before receiving the first dose of the study medication, or had undergone joint lavage and arthroscopic procedures in the previous 6 months, were also excluded.

Sponsors & Collaborators

• Sadat City University: lead

Study Sites (1)

Faculty of Pharmacy

Shibīn al Kawm, Menoufia, 13829, Egypt

Location

MeSH Terms

Interventions

Metformin

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: Principle Investigator

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 23, 2021
• Study Start: February 16, 2021
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

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

Locations

EG (1)