Osteoarthritis of the hand Musculoskeletal Diseases Arthrosis
Conditions
Interventions
Current intervention as of 26/08/2025:
RAMBOH-1 is a two-arm double-blind randomised controlled proof of concept study using a pharmacological intervention. The study will take place in selected UK NH
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 79 Years
Inclusion criteria
Inclusion criteria: 1. Participant is able to understand English and is willing and able to give written informed consent for participation in the study including to provide blood samples and donate tissue sample at surgery 2. Male or female, aged 18 to 75 years - updated 17/02/2025: aged 18-79 years 3. Symptomatic and radiographic thumb carpometacarpal (CMC) joint osteoarthritis scheduled for trapeziectomy surgery as part of usual care 4. Female participants fulfil either of these criteria: 4.1 Are of nonchildbearing potential, defined as: - Aged 45 or over and definitely postmenopausal (defined as > = 2 years without any menses) prior to screening OR - Documented as surgically sterile 4.2 Are of childbearing potential and fulfil all four of these criteria as well as the fifth, where relevant: - Are not pregnant and have a negative pregnancy test at screening, and - Agree not to try to become pregnant during the study and for 33 days after the final study medication administration, and - Agree not to breastfeed from screening until 33 days after the final study medication administration. - Agree not to donate ova from screening until 33 days after the final study medication administration. - If heterosexually active, agree to consistently use one form of highly effective birth control from screening until 33 days after the final study medication administration. 5. Male participants fulfil both of these criteria: 5.1 They and their female spouse/partner(s) who are of childbearing potential agree to use 1 form of highly effective birth control from screening until 93 days after the final study medication administration. 5.2 They agree not to donate sperm from screening until 93 days after the final study medication administration. 6. The participant agrees not to consume grapefruit or grapefruit juice for the duration of the study 7. In the Investigator’s opinion, is able and willing to comply with all study requirements
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 25/06/2025: 1. Other cause of hand pain including inflammatory arthritis (such as rheumatoid arthritis, psoriatic arthritis, gout) 2. Use of one or more prohibited treatments within specified timeframe prior to screening, or not willing to avoid treatment for the duration of the study and for 75 hours after last dose: In the last 3 years: 2.1 The retinoid medicine acitretin In the last 3 months: 2.2. Retinoids (other than acitretin) or preparations containing high doses of vitamin A 2.3. Systemic immunomodulatory therapy (including systemic corticosteroids, methotrexate, sulfasalazine, hydroxychloroquine or cyclosporin) In the last 6 weeks: 2.4. Initiation of or change to systemic hormone replacement therapy (HRT) or the combined oral contraceptive pill 2.5. Intra-articular steroid injection to the thumb CMC joint scheduled to undergo surgery Currently receiving treatment with: 2.6. the following anticonvulsants: phenytoin, carbamazepine, oxcarbazepine, phenobarbital and other barbiturates 2.7. the following antifungals: ketoconazole, itraconazole, voriconazole, fluconazole 2.8. the following anti-retrovirals: ritonavir, indinavir, saquinavir, nelfinavir, efavirenz, nevirapine 2.9. the following antibiotics: erythromycin, telithromycin, troleandomycin, clarithromycin; rifampicin, rifabutin, isoniazid 2.10. the following calcium channel blockers: mibefradil, verapamil, diltiazem 2.11. coumarin anticoagulants including warfarin 2.12. certain antiemetics: netupitant, aprepitant 2.13. the following diabetic therapies: pioglitazone, troglitazone 2.14. the following antidepressants: nefazodone, St John’s wort 2.15. the following other agents: conivaptan, modafinil 3. Presence of one or more medical contraindications to the use of talarozole or placebo: 3.1. Known hypersensitivity to drug or excipients in active medication or placebo (gelatin, polyethylene glycol (PEG) 400, PEG 4000) 3.2. Liver function tests (any of alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase) > 1.5 times the upper limit of normal at screening or within 4 weeks of screening¥ orhistory of underlying disorder likely to affect liver function during the study (not including gallbladder disease). 3.3. Estimated glomerular filtration rate of 6.0 mmol/L or a fasting triglyceride level of >3.5 mmol/L)¥ or commensurate increases in non-fasting levels 5. Bone marrow disorder or clinically significant abnormality on full blood count at screening or within 4 weeks of screening¥. 6. Chronic pancreatitis 7. Active malignancy or a history of malignancy (except for treated nonmelanoma skin cancer) within the past 5 years, OR any form of chemotherapy. 8. Recent history of active cardiovascular disease (within the last 12 months) including clinically significant arrhythmias, symptomatic ischaemic heart disease, myocardial infarction or heart failure (excluding effect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure: The difference in mean cartilage expression of a panel of pre-defined inflammatory gene mRNA levels (including, but not limited to ADAMTS4, MMP13 and MMP1) when comparing the intervention and placebo arms using a tissue sample collected at Visit 3 Day of Surgery _____ Previous primary outcome measure: Mean cartilage expression of a panel of pre-defined atRA-responsive genes mRNA levels (including, but not limited to CYP19A, CYP26A, RARa, RARß, and RAR?) using a tissue sample collected at Visit 3 Day of Surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/01/2024: 1. Mean levels of cartilage expression of atRA associated genes (including, but not limited to CYP19A, CYP26A, RARa, RARß, and RAR?) using a tissue sample collected at Visit 3 Day of Surgery 2. Mean levels of cartilage expression of atRA responsive or inflammatory response genes when considering ALDH1A2 genotype using a tissue sample collected at Visit 3 Day of Surgery 3. Mean levels of Synovial fluid and blood (plasma and cellular) molecular outcomes which may include inflammatory genes and response proteins, retinoic acid and drug levels using synovial fluid collected from the thumb CMC joint where available at Visit 3 Day of Surgery prior to excision of joint and blood samples collected at Visit 1 Screening and Visit 3 Day of Surgery. 4. Average daily hand pain on numerical rating scale (NRS), recorded by paper diary for up to 4 weeks ahead of surgery 5. Patient Evaluation Measure (PEM) at Visit 1 Screening, Visit 2 Baseline (Day 0) and at Visit 3 Day of Surgery visit (immediately before surgery) 6. Quality of life (EQ-5D-5L) at Visit 1 Screening, Visit 2 Baseline (Day 0) and at Visit 3 Day of Surgery visit (immediately before surgery) 7. Recruitment and randomisation rates using study records until end of randomisation 8. Acceptability to patients (% dropouts), collected throughout the study 9. Acceptability of study medication assessed by End of Study questionnaire and adverse events (AEs) at Visit 4 Post-surgery follow-up (at 4 weeks) and Safety Reporting Window _____ Previous secondary outcome measures: 1. Mean levels of cartilage expression of inflammatory response genes (including, but not limited to HAS1, IL6, NGF, and ADAMTS4) using a tissue sample collected at Visit 3 Day of Surgery 2. Mean levels of cartilage expression of atRA responsive or inflammatory response genes when considering ALDH1A2 genotype using a tissue sample collected at Visit 3 Day of Surgery 3. Mean levels of synovial fluid molecu | — |
Countries
England, United Kingdom
Outcome results
None listed