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.
Have given written informed consent to participate.
Be aged between 50 and 80 years (inclusive) at the time of the screening visit.
Be a fluent English speaker.
Have a diagnosis of clinically established early PD according to the Movement Disorder Society Criteria for Clinically Established Early Parkinson's Disease.
Low affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.
Any use of immunomodulatory drugs or biologic agents (such as azathioprine, mycophenolate, methotrexate, ciclosporin, cyclophosphamide etc.) within 12 months prior to screening visit, or between screening and baseline.
Any previous use of rituximab or alemtuzumab at any time.
Treatment with oral corticosteroids for greater than 2 weeks within 12 months prior to screening visit, or any oral or injected steroid use within 3 months prior to screening visit, or between screening and baseline.
Parallel
dapansutrile
DrugDapansutrile tablets administered for 26 weeks, starting at 1,000 mg daily (500 mg twice daily) for 4 weeks, escalated to 2,000 mg daily (1,000 mg twice daily) thereafter.
placebo
DrugMatched placebo tablets administered for 26 weeks, admistered as per the active treatment.
Number of adverse events (AEs) recorded during the 6-month double-blind period
Adverse events are recorded from the point of participant informed consent and at every trial visit
Change in [¹⁸F]-DPA-714 PET non-displaceable binding potential in subcortical and cortical regions of interest
Measured using PET- magnetic resonance (MR) brain imaging with \[¹⁸F\]-DPA-714, a TSPO ligand.
Change in concentration of C-reactive protein (CRP) in blood
Change in concentration of interleukin (IL)-1β in blood
Change in concentration of interferon (IFN)-γ in blood
Number of AEs recorded
Change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I
Part I of the MDS-UPDRS assesses Non-Motor Aspects of Experiences of Daily Living (nM-EDL). Scoring ranges from 0 to 52, with higher scores indicating more severe symptoms.
Change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II
Part II of the MDS-UPDRS assesses Motor Aspects of Experiences of Daily Living (M-EDL). Scoring ranges from 0 to 52, with higher scores indicating more severe symptoms.
Change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III
MDS-UPDRS part III will be used to measure the change in motor examination. Scoring ranges from 0 to 132, with a higher score indicating more severe motor impairment.
Click on the lead sponsor to view all of their trials.
Cambridge University Hospitals NHS Foundation Trust
Lead sponsor
University of Cambridge
Collaborator
Olatec Therapeutics LLC
Collaborator
Cure Parkinson's
Collaborator
Van Andel Research Institute
Collaborator
