Parkinson’s disease with mild cognitive impairment (PD-MCI) is common, has important clinical consequences, and there is currently no treatment available. Thus, there is an unmet clinical need to treat PD-MCI. The underlying pathology of cognitive impairment in Parkinson’s indicates nicotinic agonists as particularly relevant for this condition, and pro-cognitive effects of nicotinic agonists have been demonstrated in animal models, neuropsychiatric diseases, and - as a secondary outcome - indications of effect were observed on motor symptoms in Parkinson's.
What is the purpose of this study?
AZD0328 is a new drug thought to improve memory, learning and thought processes. The medication is not currently available, but has been tested in animals, healthy volunteers and people with schizophrenia. The purpose of this study is to test if AZD0328 might be of benefit in Parkinson’s, as it activates alpha-7 nicotinic receptors that are decreased in some areas of the brain in people living with Parkinson’s. This 12-week study will investigate for the first time how safe, tolerable and effective AZD0328 is in people living with Parkinson’s who also have ‘mild cognitive impairment’. The study is called PD-MIND and stands for: Parkinson’s disease with mild cognitive impairment treated with nicotinic agonist drug.
The study aims to identify the most relevant cognitive areas improved by AZD0328, and the underlying mechanisms involved. The study will assess magnetic resonance imaging (MRI) imaging biomarkers, to discover potential predictors of response to AZD0328, markers of target involvement and disease progression.
PD-MIND is a phase 2a, randomized, double-blind, placebo-controlled, parallel-group designed study. It is an international multi-centre study with 10 study sites in Europe: UK, Italy, Germany, Czech Republic and Norway. 160 individuals with PD-MCI will be recruited and randomised: 80 in active (AZD0328) group and 80 in control (placebo) group. A subset of 90 participants will have an MRI scan at study entry and exit to compare pictures of the brain before and after taking study medication.
The study is a multi-centred, randomized, double-blind, placebo-controlled, parallel-group, Phase II study of AZD0328 in PD-MCI. The study will be conducted at sites across Europe: UK, Italy, Germany, Czech Republic and Norway. 160 individuals with mild to moderate PD will be randomized to receive 1mg of AZD0328 or placebo (dummy drug) for 12 weeks. After screening, study participants will complete assessments, ratings scales, computer-based cognitive tasks and undergo health checks at 3 visits at 6-week intervals. 90 participants will also have MRI scans at study entry and study exit, to compare pictures of the brain before and at end of treatment.
Impact on Parkinson’s disease:
There is the prospect of discovering new biomarkers for PD-MCI, important for detecting and monitoring the disease course in general. The MRI biomarkers assessed may have the potential to identify subgroups with high or low likelihood of response to nicotinic agents (i.e. “diagnostic MRI biomarker tools”). These could be further developed towards an opportunity for personalized medical interventions.
Being a Phase 2a study, the study is an exploratory rather than confirmatory study to assess whether a reasonably strong signal of efficacy can be achieved. Moreover, monitoring treatment effects using structural and functional MRI is in infancy. If successful, the findings will inform phase III clinical trial designs.