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

Osteo Arthritis Knee Clinical Trial

Official title:

The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Patients With Knee Osteoarthritis: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04767841
• Other study ID #: 10/2021RHU
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 16, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2023
• Source: Sadat City University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Metformin
Metformin 1000mg tablet plus celecoxib 200 mg capsule
• Placebo
Placebo tablet plus celecoxib 200 mg capsule

Locations

Country	Name	City	State
Egypt	Faculty of Pharmacy	Shibin Al Kawm	Menoufia

Sponsors (1)

Lead Sponsor	Collaborator
Sadat City University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue scale assessment of pain	the change of Visual Analogue Scale (VAS) pain score from baseline to posttreatment	week 12
Secondary	WOMAC change	the change of WOMAC Osteoarthritis Index from baseline to posttreatment	week 12
Secondary	the change of Short Form 36 Questionnaire (SF-36) score from baseline to posttreatment	The SF-36 is a generic instrument to assess health-related quality of life. It consists of 36 questions and assesses 8 dimensions: physical functioning, role physical, pain index, general health, vitality, social functioning, role emotional, and mental health index. It also provides 2 summary measures of physical and mental components. The SF-36 score ranges from 0 to 100, with higher scores indicating better health status.	week 12
Secondary	Adverse drug reaction	Clinical side effects	12 weeks
Secondary	AMPK expression	AMPK gene expression	12 weeks
Secondary	Serum level Tumor necrosis factor- alpha (TNF-a)	Serum level Tumor necrosis factor- alpha (TNF-a)	12 weeks
Secondary	Serum levels of IL-1ß	Serum levels of IL-1ß	12 weeks
Secondary	IL-17	Serum levels of IL-17	12 weeks