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

Phase 1
Recruiting
Conditions
Osteo Arthritis Knee
Interventions
Drug: Placebo
Registration Number
NCT04767841
Lead Sponsor
Sadat City University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo tablet daily plus Celecoxib 200mg capsule
MetforminMetforminMetformin 1000 mg daily plus Celecoxib 200mg capsule
Primary Outcome Measures
NameTimeMethod
Visual Analogue scale assessment of painweek 12

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

Secondary Outcome Measures
NameTimeMethod
AMPK expression12 weeks

AMPK gene expression

WOMAC changeweek 12

the change of WOMAC Osteoarthritis Index from baseline to posttreatment

Serum level Tumor necrosis factor- alpha (TNF-α)12 weeks

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

the change of Short Form 36 Questionnaire (SF-36) score from baseline to posttreatmentweek 12

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.

IL-1712 weeks

Serum levels of IL-17

Adverse drug reaction12 weeks

Clinical side effects

Serum levels of IL-1β12 weeks

Serum levels of IL-1β

Trial Locations

Locations (1)

Faculty of Pharmacy

🇪🇬

Shibīn Al Kawm, Menoufia, Egypt

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