Retinoic acid metabolism blocking agents to treat osteoarthritis of the hand: A 2-arm double-blind randomised controlled proof of concept study (RAMBOH-1)
The RAMBOH-1 study will test whether a type of drug called a Retinoic Acid Metabolism Blocking Agent (RAMBA) can increase retinoic acid levels and reduce inflammation in the base of the thumb joint, when compared with taking a placebo.
Participants with base of thumb osteoarthritis scheduled for trapeziectomy will take a daily RAMBA capsule for around 14 days before surgery. Changes in joint-based cell markers will be measured in spare tissue which would normally be discarded following hand surgery. The study will generate information to help plan a larger study in the future.
The joint at the base of the thumb can commonly be affected by osteoarthritis (OA) causing pain and functional difficulties for many. There are currently no drugs that can slow the progression of OA regardless of the joint(s) affected. Current treatment options may include pain relief, specific hand exercises, steroid injections, and surgery in severe cases.
Recent genetic studies have identified that individuals with severe hand OA have variation in a gene named ALDH1A2. This variation may lead to reduced production of a substance called retinoic acid (a natural anti-inflammatory agent). This decrease in retinoic acid may contribute to the progression of hand OA. Laboratory work has found that a drug known as a Retinoic Acid Metabolism Blocking Agent (RAMBA) may help to prevent breakdown of retinoic acid and have an anti-inflammatory effect.
Aims and objectives
The primary objective is to test whether a RAMBA capsule taken daily for 14 days ahead of trapeziectomy can affect retinoic acid associated gene expression in the cartilage tissue of patients with base of thumb OA, compared to placebo.
The secondary objectives are to:
- Explore other molecular outcomes
- Collect clinical outcome data to inform the design of a definitive future study
- Collect data to inform the feasibility of a definitive future study
RAMBOH-1 is a 2 arm double-blind randomised controlled proof of concept study using a pharmacological intervention.
Sample Size: 44 patients will be recruited from 2 sites in the UK: Nuffield Orthopaedic Centre, Oxford, and Wexham Park Hospital, Slough.
Population: Male or female aged 18-75 years undergoing trapeziectomy for base of thumb osteoarthritis
Study Visits: There are two study visits plus two telephone appointments over a 4-16 week period.