Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06126029
Other study ID # BSMMU/2023/11020
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 15, 2023
Est. completion date June 30, 2024

Study information

Verified date November 2023
Source Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Contact Md.Delowar Hossain, MD
Phone +8801675369860
Email delowar650@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The goal of this randomized, double blind, placebo-controlled clinical trial is to learn about, the effect of metformin compared with placebo-controlled group on disease activity and interleukin-6 level in patients with knee osteoarthritis.The main question it aims to answer is:Is Metformin as add-on therapy more effective in reducing disease activity in Ibuprofen-treated patients with grade II-III knee osteoarthritis? Half of Participants will receive metformin with standard of care(ibuprofen and rabeprazole) while other half placebo and standard of care (ibuprofen and rabeprazole).


Description:

Osteoarthritis (OA) is a worldwide highly prevalent chronic joint disease commonly affecting individuals of 40 years and older. OA is highly debilitating, encompassing various physical symptoms like pain, stiffness, swelling, disability and loss of normal joint function. Knee OA is one of the major causes of impaired function and disability of elderly population resulting in markedly reduced quality of life and increased socioeconomic burden. (OA) is a progressive degenerative disorder characterized by degraded cartilage,low to moderate synovial inflammation, alteration of bony structure.The pathogenesis of OA is complex, combination of risk factors such as aging, obesity, being female, smoking, genetics, excessive joint load and injury, metabolic alterations and mechanical stress contribute to OA.These factors induce low-grade chronic inflammation and imbalance in oxidant-antioxidant levels, stimulating chondrocytes to produce reactive oxygen species (ROS) and pro-inflammatory cytokines. Overproduction of IL-1β, IL-6, TNF-α activate synoviocytes,macrophages, B and T lymphocytes, chondrocytes to play a role in the cartilage degradation, a central feature of OA.The infrapatellar fat pad (IFP) from knee OA patients secreted significantly higher levels of IL-6, but not TNF-α and IL-1β. Decreased AMPK-α activity was found in human samples as well as mice OA knee joint chondrocytes which leads to increased mTOR activity,inhibition of autophagy, increased apoptosis and inflammatory activity of OA chondrocytes. Mitochondrial injury and a lowered expression of SIRT1 protein are often associated with the pathogenesis of OA. Existing therapies such as Nonsteroidal Anti-inflammatory drugs (NSAIDs) and other analgesics are only used to reduce pain and swelling. With the chronic nature of knee OA, pharmacological approaches must be safe for long-term use. NSAIDs are the mainstay of management for knee OA but cause serious gastrointestinal, renal and cardiovascular adverse events with no beneficial effect on joint structures.Total knee replacement is the last option for patients with end-stage knee OA. Metformin exerts a chondroprotective effect by inducing the SIRT1 expression and activating AMPK-α, leading to reduced inflammatory mediators and matrix degradation substances, inhibit the accumulation of RAGE, increase in autophagy as well as a decrease in catabolism and apoptosis, as evidenced by in vivo and in vitro studies. Metformin as an AMPK-α activator can protect inflammatory cell death of chondrocytes and attenuates cartilage degeneration and prevents or delays the development and progression of knee OA. Metformin is able to reduce RANKL and stimulates OPG expression in osteoblasts, further inhibit osteoclast differentiation and prevent bone loss. Data from human studies suggest that metformin could reduce knee OA progression by modifying inflammatory pathways and being considered as an alternative or adjuvant treatment of knee OA. This study is a double-blind, randomized, placebo-controlled trial in knee OA patients. This study will be conducted to evaluate the effect of metformin as add-on therapy on disease progression and inflammatory indicator in knee OA patients.The intervention group will receive metformin 500mg extended release tablet once daily for 8 weeks, with standard of care(ibuprofen and rabeprazole) as prescribed by the physician whereas control group will receive placebo oral tablet once daily with standard of care(ibuprofen and rabeprazole) during the same study period. The investigator will compare changes in five dimensions (pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life) of KOOS score (out of 100) and serum interleukin-6 (IL-6) level, at the time of recruitment with after 8 weeks of intervention in both the intervention and placebo controlled groups. Adding Metformin with the conventional treatment of Ibuprofen could potentially have a substantial impact on disease activity in patients with Knee Osteoarthritis(OA).


Recruitment information / eligibility

Status Recruiting
Enrollment 68
Est. completion date June 30, 2024
Est. primary completion date April 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - Patients with knee pain - Radiographic evidence of knee osteoarthritis (Grade II-III) - Age 18-65 years - Both male and female - Normal BMI(for asians): 18.5-22.9 kg/m2 Exclusion Criteria: - Diagnosed case of Diabetes Mellitus, renal, hepatic, cardiovascular or pulmonary disease - Diagnosed case of Gout or pseudogout - Diagnosed case of systemic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease - Patients currently receiving immunosuppressant, carbonic anhydrase inhibitors(topiramate), ranolazine, vandetanib, dolutegravir - History of receiving a corticosteroid injection in the last three months - Prior history of knee trauma or surgery - Metformin use or history of use in the last two months - Known allergy to metformin - History of lactic acidosis - Patient with habit of excessive alcohol intake - Pregnancy - Patients unwilling to participate or unwilling to give written consent - Participation in another clinical trial

Study Design


Intervention

Drug:
Metformin 500 Mg extended release Oral Tablet
34 patients of experimental group will get metformin 500mg extended release oral tablet once daily with evening meal along with standard of care (ibuprofen 400mg and rabeprazole 20mg twice daily) for 8 weeks as prescribed by the physician.
Placebo oral tablet
34 patients of placebo group will get placebo oral tablet once daily with evening meal along with standard of care (ibuprofen 400mg and rabeprazole 20mg twice daily) for 8 weeks as prescribed by the physician.

Locations

Country Name City State
Bangladesh Bangabandhu Sheikh Mujib Medical University Dhaka

Sponsors (1)

Lead Sponsor Collaborator
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type Measure Description Time frame Safety issue
Primary Knee Injury and Osteoarthritis Outcome Score (KOOS) The KOOS meets basic criteria of outcome measures and can be used to evaluate the course of knee injury and treatment outcome. KOOS will be used to assess improvements in the scores(out of 100) of five patient-relevant outcomes (pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life) of knee osteoarthritis patients after 8 weeks of intervention. 1 year
Secondary Serum Interleukin-6 (IL-6) level The reported values for IL-6 in the blood of healthy donors varied between 0 and 43.5 pg/ml.The pooled estimate of IL-6 was 5.186 pg/ml. IL-6 follows a circadian rhythm with a peak at the time of waking (04 am).Significantly higher levels of IL-6 are secreted from the Infrapatellar fat pad of knee OA patients and correlate with disease progression or severity of cartilage pathology. 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT04651673 - Prescribed Knee Brace Treatments for Osteoarthritis of the Knee (Knee OA)
Completed NCT05677399 - Knee Osteoarthritis Treatment With Peloidotherapy and Aquatic Exercise. N/A
Active, not recruiting NCT04043819 - Evaluation of Safety and Exploratory Efficacy of an Autologous Adipose-derived Cell Therapy Product for Treatment of Single Knee Osteoarthritis Phase 1
Recruiting NCT06000410 - A Study to Evaluate the Efficacy of Amniotic Suspension Allograft in Patients With Osteoarthritis of the Knee Phase 3
Completed NCT05014542 - Needling Techniques for Knee Osteoarthritis N/A
Recruiting NCT05892133 - Prehabilitation Effect on Function and Patient Satisfaction Following Total Knee Arthroplasty N/A
Recruiting NCT05528965 - Parallel Versus Perpendicular Technique for Genicular Radiofrequency N/A
Active, not recruiting NCT03472300 - Prevalence of Self-disclosed Knee Trouble and Use of Treatments Among Elderly Individuals
Active, not recruiting NCT02003976 - A Randomized Trial Comparing High Tibial Osteotomy Plus Non-Surgical Treatment and Non-Surgical Treatment Alone N/A
Active, not recruiting NCT04017533 - Stability of Uncemented Medially Stabilized TKA N/A
Completed NCT04779164 - The Relation Between Abdominal Obesity, Type 2 Diabetes Mellitus and Knee Osteoarthritis N/A
Recruiting NCT04006314 - Platelet Rich Plasma and Neural Prolotherapy Injections in Treating Knee Osteoarthritis N/A
Recruiting NCT05423587 - Genicular Artery Embolisation for Knee Osteoarthritis II N/A
Enrolling by invitation NCT04145401 - Post Market Clinical Follow-Up Study- EVOLUTION® Revision CCK
Active, not recruiting NCT03781843 - Effects of Genicular Nerve Block in Knee Osteoarthritis N/A
Completed NCT05974501 - Pre vs Post Block in Total Knee Arthroplasty (TKA) Phase 4
Completed NCT05324163 - Evaluate Efficacy and Safety of X0002 in Treatment of Knee Osteoarthritis Phase 3
Completed NCT05529914 - Effects of Myofascial Release and Neuromuscular Training for Pes Anserine Syndrome Associated With Knee Osteoarthritis N/A
Recruiting NCT05693493 - Can Proprioceptive Knee Brace Improve Functional Outcome Following TKA? N/A
Not yet recruiting NCT05510648 - Evaluation of the Effect of High-intensity Laser Therapy in Knee Osteoarthritis N/A