Research into existing medicines to reduce aging, pain, and inflammation in osteoarthritis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2026-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective of this trial is to evaluate the potential of existing 2-drug combinations on slowing epigenetic and biological age acceleration in patients with knee osteoarthritis (OA).

Secondary objectives 1

1. The secondary objective of this trial are to determine whether existing 2-drug combinations decrease pain, inflammation, and reduce the progression of knee OA.

Conditions and MedDRA coding

Osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Written informed consent
2. Age ≥18 and <80
3. Radiological diagnosis of knee osteoarthritis according to their general practitioner and/or medical specialist (e.g. orthopaedic surgeon, rheumatologist), with a KL grade ≥ 2.
4. Ability to swallow and retain oral medication

Exclusion criteria 30

1. Known allergy or hypersensitivity to any of the medications or their excipients in the clinical trial (baricitinib, dolutegravir, metformin, colchicine)
2. A planned surgery under general, spinal, or epidural anesthesia.
3. Any type of acute metabolic acidosis (lactic acidosis, diabetic ketoacidosis).
4. Current use of one or more of the study medications for any indication (baricitinib, dolutegravir, metformin, colchicine).
5. Moderate or severe renal impairment (eGFR<50mL/min/1.73m2)
6. Liver function impairment as evidenced by serum alanine transferase (ALAT) > 3 ULN (up-per limit of normal).
7. Abnormal lymphocyte or neutrophil counts or haemoglobin levels (Lymphocyte counts <0.5 * 10^9/ul, or neutrophil counts < 1 * 10^9/µL or haemoglobin <8 mmol/L for men and <7 mmol/L for women).
8. Use of systemic immunomodulatory drugs: steroids, anti-inflammatory biological treatments (e.g., anti-cytokine monoclonal antibodies).
9. Acute or active illness within two weeks before the start of the study.
10. Received vaccination within two weeks before the start of the study.
11. Peripheral neuritis, myositis or marked myo-sensitivity to statins.
12. Male participants not willing to use effective contraception during the study to prevent pregnancy
13. Using medications that are substrates of OCT2, inhibitors of OCT1, inducers of OCT1, inhibi-tors of OCT2, inducers of OCT2, strong CYP3A4 inhibitors, strong CYP3A4 inducers, , strong OAT3 inhibitors, substrates of Pgp, and/or substrates of BCRP. A non-exhaustive list of such medications is given below; fampridine (or dalfampridine); macrolide antibiotics (i.e. eryth-romycin, azithromycin); probenecid ;antimycotics (i.e. ketoconazole, fluconazole, itracona-zole, posaconazole and voriconazole); antimycobacterials (rifabutin, rifampicin); anticon-vulsants (carbamazepine, oxcarbazepine, phenytoin, phenobarbital); protease inhibitors & anti-retroviral drugs (i.e. boceprevir, nelfinavir ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir, and cobicistat); anti-arrhythmic drugs (i.e. verapamil, dilti-azem); immunosuppressants (i.e. cyclosporine); hepatitis C drug telaprevir; atypical antide-pressant nefazodone and herbal product St. John’s wort.
14. Other known medical diseases that may affect joints.
15. Known generalized pain syndromes such as fibromyalgia.
16. High frailty (Clinical Frailty Scale ≥ 7) or predicted life expectancy < 5 years.
17. Current enrollment in another trial.
18. Incapacitated patients.
19. Pregnant or breastfeeding females.
20. Fertile female participants not taking sufficient contraception.
21. Having had a diagnosis of depression.
22. Immunodeficiencies and autoimmune diseases.
23. Acute and unstable heart failure.
24. Alcohol addiction (i.e. >14 units per week).
25. Current or past long-time smokers (i.e. one or more cigarettes per day).
26. Having had hepatitis B or tuberculosis.
27. Having had cancer.
28. A planned imaging procedure involving the intravascular administration of iodinated contrast agents
29. Having had Herpes zoster.
30. Having had venous thromboembolism.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in epigenetic and biological age acceleration before and after medication use.

Secondary endpoints 3

1. Change in inflammatory proteins and cytokines in the circulation before and after medication use.
2. Change in pain severity and the knee osteoarthritis biomarkers in the blood and urine before and after medication use.
3. Safety of the drug combinations assessed by the proportion of treatment emergent adverse events and grade 3/4 laboratory abnormalities.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Calin Popa

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Calin Popa

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications