Retinoic acid metabolism blocking agents (RAMBAs) to treat hand osteoarthritis: A 2-arm double-blind randomised controlled proof of concept study (RAMBOH-1)

Research summary

The base of thumb joint can commonly be affected by osteoarthritis (OA). This can lead to pain, stiffness, swelling, and difficulty performing activities such as writing, opening jars, or turning keys. Treatment options may include advice on lifestyle factors that may contribute, hand exercises, pain relief such as anti-inflammatory gels or paracetamol, splints, and steroid injections. A surgical procedure called a trapeziectomy (removal of the trapezium bone at the base of the thumb) may be performed where there is ongoing pain and/or severe disability after trying other more conservative treatments. There are currently no drugs that can slow the progression of OA. Recent genetic studies have shown that some individuals with severe hand OA have variation in a gene named ALDH1A2. This gene is responsible for making retinoic acid, which is a natural anti-inflammatory agent. Researchers at the University of Oxford have shown that retinoic acid levels rapidly decrease after cartilage injury, a primary cause of OA. A group of drugs known as Retinoic Acid Metabolism Blocking Agents (RAMBAs) may help to prevent this decrease in retinoic acid, and have an anti-inflammatory effect in patients with base of thumb OA. If this drug is proven to be effective it could provide a new treatment option, reducing pain, progression, and the need for surgery. The RAMBOH-1 study is an MRC funded proof-of-concept study where we will give a 2 week course of either a type of RAMBA (talarozole) or placebo capsules to up to 56 participating patients ahead of scheduled trapeziectomy surgery at selected NHS hospitals. Waste tissue from the surgery will be analysed to see if talarozole affects retinoic acid associated gene expression in the cartilage tissue of these patients. Clinical and feasibility data will also be collected to help inform and design a potential larger study in the future.

Principal Investigator

Prof Dominic Furniss

Contact us

Email: gail.lang@ndorms.ox.ac.uk

IRAS number

291242