Back to resultsEffect of Metformin on Patients With Osteoarthritis
Primary Purpose
Osteoarthritis
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Metformin hydrochloride sustained release tablets
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- Meet the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis assessed by a rheumatologist;
- Age 50 to 75 years;
- Body mass index ≥ 24 kg/m2;
- Knee pain ≥ 20 on a 100 mm visual analogue scale (VAS);
- Able to listen, speak, read and understand Chinese; capable of understanding the study requirements and willing to cooperate with the study instructions; able to provide written, informed consent.
Exclusion Criteria:
- Severe radiographic knee OA as grade 3 joint space narrowing according to the Osteoarthritis Research Society International (OARSI) atlas;
- Severe knee pain as knee pain ≥ 80 on a 100 mm VAS;
- Planned knee or hip surgery (including arthroscopy, joint replacement, and joint open operation) within 2 years;
- Severe knee trauma history (including arthroscopy, severe injury of knee ligament or meniscus);
- Contraindication to MRI scanning (e.g. implanted pacemaker, artificial metal valve or cornea, aneurysm clipping surgery, arterial dissection, metal foreign bodies in the eyeball, claustrophobia);
- Other forms of inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis);
- Active malignant cancer or other life-threatening diseases;
- Type 1 or type 2 diabetes mellitus;
- Clinical manifestation of liver dysfunction or alanine aminotransferase/aspartate aminotransferase exceeding 2 times the upper limit of normal value;
- Estimated glomerular filtration rate less than 60 ml/min/1.73 m2;
- Hypoxic state (e.g. chronic heart insufficiency, acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, cor pulmonale, peripheral vascular disease);
- Alcoholism;
- Pregnancy or lactation;
- Allergic to metformin hydrochloride;
- Conditions affecting the absorption of oral drugs (e.g. postgastrectomy and malabsorption syndrome);
- Use of metformin in recent 30 days or plan to use metformin in the next 2 years;
- Use of investigational drug in recent 30 days.
Sites / Locations
- Foshan First People's Hospital
- Guangzhou First People's HospitalRecruiting
- Liwan Central Hospital of Guangzhou
- Sun Yat-Sen Memorial Hospital
- Zhujiang Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin
Placebo
Arm Description
Metformin hydrochloride sustained release tablet will administer orally in escalating doses to reduce side-effects and maintain masking: 0.5 g/day for the first two weeks, 1 g/day for the next 2 weeks, and then 2 g/day until the end of the study if tolerated. If the subject cannot tolerate the maximum dose (2 g/day), take their maximum tolerable dose. In case of adverse reaction, the researchers can determine whether the subject needs to reduce or stop the drug based on their discretion.
Placebo will administer the same as the experimental drug.
Outcomes
Primary Outcome Measures
Change of tibiofemoral cartilage volume from baseline to 24 months follow up
Cartilage volume will be automatically calculated based on a standardized view of 3D cartilage geometry by OsiriX software (University of Geneva, Geneva, Switzerland). The 3D cartilage geometry is composed from the 2D cartilage shapes, which are generated by drawing contours around the cartilage boundaries on section-by-section MR images. Tibiofemoral cartilage volume will be calculated as the sum of both the tibial and femoral compartments.
Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up
The WOMAC system in a 100-mm visual analog format will be used to quantify the degree of knee pain (5 questions), joint stiffness (2 questions), and physical dysfunction (17 questions) during the last 7 days. The WOMAC score will be calculated by summing the score of each question (1 point for every 1 mm), and a higher score of WOMAC represents a severe OA symptom. The WOMAC score will be considered invalid and treated as missing data if more than 5 of the questions are not answered. In case no more than 5 items are missed, the remaining items will be averaged and then multiplied by 24 to create the WOMAC score.
Secondary Outcome Measures
Change of knee pain visual analog scale from baseline to 24 months follow up
The 100 mm VAS will be used to assess the knee pain during the last 7 days, and a higher VAS indicates a severe knee pain.
Change of tibiofemoral cartilage defect from baseline to 24 months follow up
Cartilage defects will be graded using a modified Outerbridge classification as follows: grade 0, normal cartilage; grade 1, focal blistering and intra-cartilaginous hyperintensity with a normal contour; grade 2, irregularities on the surface and loss of thickness of less than 50%; grade 3, deep ulceration with loss of thickness of more than 50% without exposure of subchondral bone; grade 4, full-thickness chondral wear with exposure of subchondral bone. Cartilage defects will be assessed at the medial tibial, medial femoral, lateral tibial, and lateral femoral compartments, and tibiofemoral cartilage defects will be obtained by summing the scores of the four compartments.
Change of effusion-synovitis volume from baseline to 24 months follow up
Effusion-synovitis volume will be measured at suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess according to the anatomy of the knee joint synovial cavity. Effusion synovitis will be isolated by selecting a region of interest with an intra-articular fluid-equivalent signal on the section-by-section 2D MR images. The volume of effusion-synovitis will be generated using OsiriX software. Total effusion-synovitis volume of the knee will be obtained by summing the volume of possible effusion synovitis in the four synovial cavities.
Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up
Bone marrow lesions is defined as discrete areas of increased signal in the subchondral bone. Bone marrow lesions maximum size will be assessed at the medial tibial, medial femoral, lateral tibial, and lateral femoral compartments. Slice with the greatest area of bone marrow lesions in a specific compartment will be chosen to assess bone marrow lesions maximum size of the corresponding compartment. Bone marrow lesions on adjacent slices will be measured and compared to locate the slice with the maximum lesion size. Tibiofemoral bone marrow lesions maximum size will be calculated by summing the maximum lesions size of the four compartments.
Full Information
NCT ID
NCT05034029
First Posted
August 25, 2021
Last Updated
December 16, 2021
Sponsor
Guangzhou First People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05034029
Brief Title
Effect of Metformin on Patients With Osteoarthritis
Official Title
Effect of Metformin on Tibiofemoral Cartilage Volume and Knee Symptoms Among Overweighted Knee Osteoarthritis patients-a Randomized Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangzhou First People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
This randomized controlled trial aims to investigate if metformin has osteoarthritis protective effects among overweighted knee osteoarthritis patients. The co-primary outcomes are changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Arthritis Index (WOMAC) from baseline to month 24. The secondary outcomes are changes in visual analog scale (VAS)-assessed knee pain, tibiofemoral cartilage defect, effusion-synovitis volume, and tibiofemoral bone marrow lesion maximum size from baseline to month 24.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
262 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin hydrochloride sustained release tablet will administer orally in escalating doses to reduce side-effects and maintain masking: 0.5 g/day for the first two weeks, 1 g/day for the next 2 weeks, and then 2 g/day until the end of the study if tolerated. If the subject cannot tolerate the maximum dose (2 g/day), take their maximum tolerable dose. In case of adverse reaction, the researchers can determine whether the subject needs to reduce or stop the drug based on their discretion.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will administer the same as the experimental drug.
Intervention Type
Drug
Intervention Name(s)
Metformin hydrochloride sustained release tablets
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change of tibiofemoral cartilage volume from baseline to 24 months follow up
Description
Cartilage volume will be automatically calculated based on a standardized view of 3D cartilage geometry by OsiriX software (University of Geneva, Geneva, Switzerland). The 3D cartilage geometry is composed from the 2D cartilage shapes, which are generated by drawing contours around the cartilage boundaries on section-by-section MR images. Tibiofemoral cartilage volume will be calculated as the sum of both the tibial and femoral compartments.
Time Frame
Baseline and 24 months follow up
Title
Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up
Description
The WOMAC system in a 100-mm visual analog format will be used to quantify the degree of knee pain (5 questions), joint stiffness (2 questions), and physical dysfunction (17 questions) during the last 7 days. The WOMAC score will be calculated by summing the score of each question (1 point for every 1 mm), and a higher score of WOMAC represents a severe OA symptom. The WOMAC score will be considered invalid and treated as missing data if more than 5 of the questions are not answered. In case no more than 5 items are missed, the remaining items will be averaged and then multiplied by 24 to create the WOMAC score.
Time Frame
Baseline and 3, 6, 12, 24 months follow up
Secondary Outcome Measure Information:
Title
Change of knee pain visual analog scale from baseline to 24 months follow up
Description
The 100 mm VAS will be used to assess the knee pain during the last 7 days, and a higher VAS indicates a severe knee pain.
Time Frame
Baseline and 3, 6, 12, 24 months follow up
Title
Change of tibiofemoral cartilage defect from baseline to 24 months follow up
Description
Cartilage defects will be graded using a modified Outerbridge classification as follows: grade 0, normal cartilage; grade 1, focal blistering and intra-cartilaginous hyperintensity with a normal contour; grade 2, irregularities on the surface and loss of thickness of less than 50%; grade 3, deep ulceration with loss of thickness of more than 50% without exposure of subchondral bone; grade 4, full-thickness chondral wear with exposure of subchondral bone. Cartilage defects will be assessed at the medial tibial, medial femoral, lateral tibial, and lateral femoral compartments, and tibiofemoral cartilage defects will be obtained by summing the scores of the four compartments.
Time Frame
Baseline and 24 months follow up
Title
Change of effusion-synovitis volume from baseline to 24 months follow up
Description
Effusion-synovitis volume will be measured at suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess according to the anatomy of the knee joint synovial cavity. Effusion synovitis will be isolated by selecting a region of interest with an intra-articular fluid-equivalent signal on the section-by-section 2D MR images. The volume of effusion-synovitis will be generated using OsiriX software. Total effusion-synovitis volume of the knee will be obtained by summing the volume of possible effusion synovitis in the four synovial cavities.
Time Frame
Baseline and 24 months follow up
Title
Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up
Description
Bone marrow lesions is defined as discrete areas of increased signal in the subchondral bone. Bone marrow lesions maximum size will be assessed at the medial tibial, medial femoral, lateral tibial, and lateral femoral compartments. Slice with the greatest area of bone marrow lesions in a specific compartment will be chosen to assess bone marrow lesions maximum size of the corresponding compartment. Bone marrow lesions on adjacent slices will be measured and compared to locate the slice with the maximum lesion size. Tibiofemoral bone marrow lesions maximum size will be calculated by summing the maximum lesions size of the four compartments.
Time Frame
Baseline and 24 months follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Meet the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis assessed by a rheumatologist;
Age 50 to 75 years;
Body mass index ≥ 24 kg/m2;
Knee pain ≥ 20 on a 100 mm visual analogue scale (VAS);
Able to listen, speak, read and understand Chinese; capable of understanding the study requirements and willing to cooperate with the study instructions; able to provide written, informed consent.
Exclusion Criteria:
Severe radiographic knee OA as grade 3 joint space narrowing according to the Osteoarthritis Research Society International (OARSI) atlas;
Severe knee pain as knee pain ≥ 80 on a 100 mm VAS;
Planned knee or hip surgery (including arthroscopy, joint replacement, and joint open operation) within 2 years;
Severe knee trauma history (including arthroscopy, severe injury of knee ligament or meniscus);
Contraindication to MRI scanning (e.g. implanted pacemaker, artificial metal valve or cornea, aneurysm clipping surgery, arterial dissection, metal foreign bodies in the eyeball, claustrophobia);
Other forms of inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis);
Active malignant cancer or other life-threatening diseases;
Type 1 or type 2 diabetes mellitus;
Clinical manifestation of liver dysfunction or alanine aminotransferase/aspartate aminotransferase exceeding 2 times the upper limit of normal value;
Estimated glomerular filtration rate less than 60 ml/min/1.73 m2;
Hypoxic state (e.g. chronic heart insufficiency, acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, cor pulmonale, peripheral vascular disease);
Alcoholism;
Pregnancy or lactation;
Allergic to metformin hydrochloride;
Conditions affecting the absorption of oral drugs (e.g. postgastrectomy and malabsorption syndrome);
Use of metformin in recent 30 days or plan to use metformin in the next 2 years;
Use of investigational drug in recent 30 days.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guangfeng Ruan, Doctor
Phone
13060627790
Ext
+86
Email
ruan1989.ok@163.com
Facility Information:
Facility Name
Foshan First People's Hospital
City
Foshan
State/Province
Guangzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dongmei Guo, Master
Facility Name
Guangzhou First People's Hospital
City
Guangzhou
ZIP/Postal Code
510180
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guangfeng Ruan, Doctor
Phone
13060627790
Ext
+86
Email
ruan1989.ok@163.com
Facility Name
Liwan Central Hospital of Guangzhou
City
Guangzhou
ZIP/Postal Code
510282
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiju Lou, Doctor
Facility Name
Sun Yat-Sen Memorial Hospital
City
Guangzhou
ZIP/Postal Code
510282
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yingqian Mo, Doctor
Facility Name
Zhujiang Hospital
City
Guangzhou
ZIP/Postal Code
510282
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan Qu, Doctor
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35598008
Citation
Ruan G, Yuan S, Lou A, Mo Y, Qu Y, Guo D, Guan S, Zhang Y, Lan X, Luo J, Mei Y, Zhang H, Wu W, Dai L, Yu Q, Cai X, Ding C. Can metformin relieve tibiofemoral cartilage volume loss and knee symptoms in overweight knee osteoarthritis patients? Study protocol for a randomized, double-blind, and placebo-controlled trial. BMC Musculoskelet Disord. 2022 May 21;23(1):486. doi: 10.1186/s12891-022-05434-2.
Results Reference
derived
Learn more about this trial
Effect of Metformin on Patients With Osteoarthritis
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