Metformin Treatment of Patients With Hand Osteoarthritis

Hand Osteoarthritis Clinical Trial

— METRO  

Official title:

Metformin Treatment of Patients With Hand Osteoarthritis: A Randomised, Placebo-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06367283
• Other study ID #: 2023-509181-38-00
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: Frederiksberg University Hospital
• Contact: Kasper Staberg Madsen
• Phone: +4538164162
• Email: kasperstabergmadsen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare metformin (2 g daily), or maximum tolerated dose, for 16 weeks with placebo as a treatment of hand osteoarthritis symptoms.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Hand OA according to the ACR criteria

3. Average finger (2 to 5) pain =4 on a 0-10 numeric rating scale (NRS where 10 is worst pain) over the past 30 days

4. Metformin naive

Exclusion Criteria:

Comorbidities

1. History of, or current signs of medical disease that may affect joints, e.g. rheumatoid arthritis, gout, psoriatic arthritis

2. Psoriasis

3. Known malignancy (except successfully treated squamous or basal cell skin carcinoma)

4. Drug or alcohol abuse in the last year

5. Existing nerve entrapment syndromes (e.g. carpal tunnel syndrome)

6. Known diabetes

7. Generalised pain syndromes such as fibromyalgia

8. Known peripheral neuropathies

9. Known allergies towards the interventions

10. Gastric bypass or other malabsorption syndrome

11. In case of pharmacological weight loss medication (e.g. glucagon like peptide-1 (GLP-1) analogues) or pharmacological osteoporosis medication, dosage must have been stable for 3 months without any plan of up-titration during the study period

12. Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or obstructs participation e.g. psychiatric disorders.

Surgical history

13. History of hand surgery in the target hand within 12 months prior to enrolment

14. History of arthroplasty, arthrodesis or surgical treatment of thumb base osteoarthritis in the target hand

Management strategies

15. Use of systemic corticosteroids equivalent of = 7.5 mg prednisolone daily within 3 months

16. Treatment with denosumab (Prolia/Xgeva)

17. Participation in experimental device or experimental drug study 3 months prior to enrolment

18. Intra-articular treatments of any kind of any joint of the target hand 3 months before inclusion

19. Current use of synthetic or non-synthetic opioids

20. Planning to start other treatment for hand OA in the study participation period

21. Planned CT scan with iodine contrast

22. Scheduled surgery on upper extremity of the target hand during study participation

23. Scheduled surgery requiring pause of metformin, e.g. surgery in general anaesthesia, during study participation

Reproductive system

24. Pregnancy

25. Planned pregnancy within the study period, 3 months after end of study treatment for female fertile participant and 6 months after end of study treatment for male participant

26. Insufficient anti-conception therapy for female fertile participants within the study period and 3 months after end of study treatment

• Sufficient anti-conception therapy consists of intra-uterine device (coil), hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections) or sexual abstinence

• Female participants are considered infertile if they are postmenopausal or if they have undergone surgical sterilisation (bilateral salpingectomy, hysterectomy or bilateral oophorectomy)

• Postmenopausal state is defined as no menses for 12 months without alternative medical cause before inclusion in the study

27. Insufficient anti-conception therapy for male participants within the study period and 6 months after end of study treatment

• Sufficient anti-conception therapy consists of condom or sexual abstinence

• Male participants are considered sterile if they have undergone surgical sterilisation (vasectomy)

28. Breast-feeding

Blood analysis

29. Positive anti-cyclic citrullinated peptide (>10 kU/L)

30. eGFR <60 ml/min/1.73 m2

31. Vitamin B12 deficiency < 200 pmol/L

32. Hba1c = 48 mmol/mol

Related Conditions & MeSH terms

• Hand Osteoarthritis
• Osteoarthritis

Intervention

Drug:
• Metformin
Metformin will be initiated at 500 mg once daily with breakfast meal. The dose will be increased with 500 mg every week until 2 g/day is reached, distributed as 1000 mg every morning and evening, together with a meal. If the subject cannot tolerate the maximum dose (2 g/day), the maximal tolerated dose will be given. The treatment period including titration is 16 weeks.
• Placebo
Participants in the placebo group will receive a placebo tablet identical to the metformin tablet

Locations

Country	Name	City	State
Denmark	The Parker Institute, Bispebjerg and Frederiksberg hospital	Copenhagen	Frederiksberg

Sponsors (1)

Lead Sponsor	Collaborator
Marius Henriksen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stiffness of both hands	Change in stiffness of both hands measured on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) stiffness subscale	Week 16
Other	Composite of pain, function and stiffness	Change in pain, function and stiffness of both hands measured composite on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) Hand Index Score	Week 16
Other	Physical function	Change in physical function of both hands assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI)	Week 16
Other	Physician global assessment	Change in physician global assessment of disease activity of hand OA in the target hand measured on a Visual Analogue Scale (VAS) scale	Week 16
Other	Swollen joint count	Change in physician swollen joint count of the target hand	Week 16
Other	Fatigue	Change in fatigue measured on a Visual Analogue Scale (VAS) scale	Week 16
Other	Sleep quality	Change in sleep quality measured on the Pittsburgh Sleep Quality Index (PSQI)	Week 16
Other	Absence or presence of inflammation of target hand	Change in absence or presence of inflammation of the target hand as measured by ultrasound (US)	Week 16
Other	Change in use of analgesics	Change in use of analgesics measured as the use of paracetamol and NSAIDS	Week 16
Other	Inflammatory biomarker	Change in hsCRP mg/L	Week 16
Other	Metabolic outcomes	Change in HbA1c mmol/mol	Week 16
Other	Metabolic outcomes	Change in lipids mmol/L	Week 16
Other	Vitamin K	Change in vitamin K and dephospho-uncarboxylated matrix Gla-protein ((dp)ucMGP) pmol/L	Week 16
Other	Proteomics	Change in mass-spectrometry based proteomics	Week 16
Primary	Finger pain	Change from baseline in Visual Analogue Scale (VAS) finger joint pain of the target hand after 16 weeks of treatment	Week 16
Secondary	Function	Change from baseline after 16 weeks of treatment in physical function assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) physical function subscale	Week 16
Secondary	Thumb base pain	Change from baseline after 16 weeks of treatment in Visual Analogue Scale thumb base pain of the target hand	Week 16
Secondary	Hand pain	Change from baseline after 16 weeks of treatment in pain of both hands assessed by Australian/Canadian Osteoarthritis Hand Index hand pain subscale	Week 16
Secondary	Physician tender joint count	Change from baseline after 16 weeks of treatment in joint activity of the target hand assessed by physician tender joint count	Week 16
Secondary	Patient global assessment	Change from baseline after 16 weeks of treatment in Visual Analogue Scale patient global assessment	Week 16
Secondary	Quality of life assessed by the European Quality of life - 5 dimensions (EQ-5D) scale	Change from baseline after 16 weeks of treatment in quality of life assessed by the European Quality of life - 5 dimensions scale	Week 16
Secondary	Hand strength	Change from baseline after 16 weeks of treatment in hand strength of the target hand assessed by a grip dynamometer	Week 16
Secondary	Number of treatment responders	Responders will be identified according to OMERACT-OARSI criteria, defined as (1) improvement in finger pain (primary outcome) or function (secondary outcome) =50% and an absolute change =20 mm; or (2) improvement of =20% with an absolute change =10 mm in at least two of the following three: finger pain (primary outcome), function (secondary outcome), and patient global assessment (secondary outcome).	Week 16