A Trial to Test the Use of Dapansutrile, an Anti-inflammatory Medication, in People With Parkinson's Disease

In Parkinson's disease (PD), there is inflammation in the brain, the gut and the blood, which is thought to contribute to the development and progression of the disease. The Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex of proteins which plays a critical role in mediating inflammation, and there is growing evidence from laboratory research that the inflammasome plays a role in Parkinson's disease. Dapansutrile is a new drug which has a highly specific effect on the NLRP3 inflammasome. In animal models, dapansutrile can protect against inflammation in the brain and prevent loss of dopamine cells. Initial 'in human' studies have indicated that this drug can effectively reduce inflammation without causing significant side effects. The goal of this clinical trial is to test whether dapansutrile might be a useful treatment for Parkinson's disease. The main questions it aims to answer are: 1. is dapansutrile safe and well-tolerated in people with Parkinson's? 2. does dapansutrile reduce inflammation in the brain, cerebrospinal fluid (CSF) and blood? Changes in clinical symptoms will also be measured over the course of the trial. Researchers will compare dapansutrile to a placebo (a look-alike substance that contains no drug) to see whether it is safe and what effects it has on inflammation and on clinical symptoms. Participants will be asked to take dapansutrile or a placebo every day for 6 months. Following this, all participants will be given the option to take dapansutrile every day for an additional 6 months. Participants will visit the study centre regularly throughout the trial for check-ups and blood tests. They will have a brain scan before starting treatment and again after 5-6 months. They will also be asked to have a lumbar puncture at the beginning of the trial, after 6 months of treatment and after 12 months of treatment.