OsteoarthritisNCT05034029
Effect of Metformin on Patients With Osteoarthritis
A study testing Metformin hydrochloride sustained release tablets in people with Osteoarthritis, run by Guangzhou First People's Hospital at 5 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- Metformin hydrochloride sustained release tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 262 participants
- Where
- 5 sitesChina
- Study dates
- 1 Aug 2021to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites, 5 recruiting
- Not yet recruiting
Foshan First People's Hospital
Foshan, Guangzhou
Dongmei Guo, Master
- Recruiting
Guangzhou First People's Hospital
Guangzhou, 510180
Guangfeng Ruan, Doctor, 13060627790 ext. +86, ruan1989.ok@163.com
- Not yet recruiting
Liwan Central Hospital of Guangzhou
Guangzhou, 510282
Aiju Lou, Doctor
- Not yet recruiting
Sun Yat-Sen Memorial Hospital
Guangzhou, 510282
Yingqian Mo, Doctor
- Not yet recruiting
Zhujiang Hospital
Guangzhou, 510282
Yuan Qu, Doctor
About this study
Official title: 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.
- Conditions
- Osteoarthritis
- Being tested
- Metformin hydrochloride sustained release tablets, Placebo
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin hydrochloride sustained release tabletsDrug
Oral
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | 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. Receives: Drug: Metformin hydrochloride sustained release tablets |
| Placebo | Placebo comparator | Placebo will administer the same as the experimental drug. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 24 months follow up
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.
Measured: Baseline and 3, 6, 12, 24 months follow up
Secondary outcomes (4)
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.
Measured: Baseline and 3, 6, 12, 24 months follow up
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.
Measured: Baseline and 24 months follow up
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.
Measured: Baseline and 24 months follow up
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.
Measured: Baseline and 24 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start1 Aug 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 262 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou First People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05034029
- Sponsor's protocol ID
- K-2021-001-02
- Status last verified
- Aug 2021
- First submitted
- 25 Aug 2021
- Last updated
- 6 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35598008
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin on Tibiofemoral Cartilage Volume and Knee Symptoms Among Overweighted Knee Osteoarthritis patients-a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05034029
- Acronym / sponsor ID
- K-2021-001-02
- Conditions
- Osteoarthritis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 262 participants (estimated)
- Lead sponsor
- Guangzhou First People's HospitalUniversity, hospital or other
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 5 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin hydrochloride sustained release tabletsMetformin 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 | Placebo comparator | Drug: PlaceboPlacebo will administer the same as the experimental drug. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (17 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin hydrochloride sustained release tabletsOral | Drug | Metformin |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
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.
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.
4 secondary outcomes
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
Change of tibiofemoral cartilage defect from baseline to 24 months follow up
Time frame: 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
Change of tibiofemoral bone marrow lesion maximum size from baseline to 24 months follow up
Time frame: Baseline and 24 months follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
- Derived from this study: PubMed 35598008Ruan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin hydrochloride sustained release tablets in people with Osteoarthritis, run by Guangzhou First People's Hospital at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guangfeng Ruan, Doctor (13060627790 ext. +86, ruan1989.ok@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of tibiofemoral cartilage volume from baseline to 24 months follow up (time frame: Baseline and 24 months follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05034029, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2022.