Effect of Metformin on Patients With Osteoarthritis

December 16, 2021 updated by: Guangzhou First People's Hospital

Effect of Metformin on Tibiofemoral Cartilage Volume and Knee Symptoms Among Overweighted Knee Osteoarthritis patients-a Randomized Clinical Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
262

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Guangzhou, China, 510180
        • Recruiting
        • Guangzhou First People's Hospital
        • Contact:
      • Guangzhou, China, 510282
        • Not yet recruiting
        • Liwan Central Hospital of Guangzhou
        • Contact:
          • Aiju Lou, Doctor
      • Guangzhou, China, 510282
        • Not yet recruiting
        • Sun Yat-sen Memorial Hospital
        • Contact:
          • Yingqian Mo, Doctor
      • Guangzhou, China, 510282
        • Not yet recruiting
        • Zhujiang Hospital
        • Contact:
          • Yuan Qu, Doctor
    • Guangzhou
      • Foshan, Guangzhou, China
        • Not yet recruiting
        • Foshan First People's Hospital
        • Contact:
          • Dongmei Guo, Master

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Meet the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis assessed by a rheumatologist;
  2. Age 50 to 75 years;
  3. Body mass index ≥ 24 kg/m2;
  4. Knee pain ≥ 20 on a 100 mm visual analogue scale (VAS);
  5. 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:

  1. Severe radiographic knee OA as grade 3 joint space narrowing according to the Osteoarthritis Research Society International (OARSI) atlas;
  2. Severe knee pain as knee pain ≥ 80 on a 100 mm VAS;
  3. Planned knee or hip surgery (including arthroscopy, joint replacement, and joint open operation) within 2 years;
  4. Severe knee trauma history (including arthroscopy, severe injury of knee ligament or meniscus);
  5. 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);
  6. Other forms of inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis);
  7. Active malignant cancer or other life-threatening diseases;
  8. Type 1 or type 2 diabetes mellitus;
  9. Clinical manifestation of liver dysfunction or alanine aminotransferase/aspartate aminotransferase exceeding 2 times the upper limit of normal value;
  10. Estimated glomerular filtration rate less than 60 ml/min/1.73 m2;
  11. Hypoxic state (e.g. chronic heart insufficiency, acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, cor pulmonale, peripheral vascular disease);
  12. Alcoholism;
  13. Pregnancy or lactation;
  14. Allergic to metformin hydrochloride;
  15. Conditions affecting the absorption of oral drugs (e.g. postgastrectomy and malabsorption syndrome);
  16. Use of metformin in recent 30 days or plan to use metformin in the next 2 years;
  17. Use of investigational drug in recent 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Metformin
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.
Drug: Metformin hydrochloride sustained release tablets
Oral
Placebo Comparator: Placebo
Placebo will administer the same as the experimental drug.
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of tibiofemoral cartilage volume from baseline to 24 months follow up
Time Frame: Baseline and 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.
Baseline and 24 months follow up
Change of Western Ontario and McMaster Universities Osteoarthritis Index from baseline to 24 months follow up
Time Frame: Baseline and 3, 6, 12, 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.
Baseline and 3, 6, 12, 24 months follow up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of knee pain visual analog scale from baseline to 24 months follow up
Time Frame: Baseline and 3, 6, 12, 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.
Baseline and 3, 6, 12, 24 months follow up
Change of tibiofemoral cartilage defect from baseline to 24 months follow up
Time Frame: Baseline and 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.
Baseline and 24 months follow up
Change of effusion-synovitis volume from baseline to 24 months follow up
Time Frame: Baseline and 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.
Baseline and 24 months follow up
Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up
Time Frame: Baseline and 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.
Baseline and 24 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guangzhou First People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 25, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 6, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • K-2021-001-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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