Study Rationale:
Parkinson’s disease with mild cognitive impairment (PD-MCI) is common, has important clinical consequences, and there is currently no treatment available. The underlying pathology of cognitive impairment in Parkinson’s disease (PD) indicates nicotinic agonists as particularly relevant for this condition, and pro-cognitive effects of nicotinic agonists have been demonstrated in models. And these drugs also had an effect on motor symptoms in PD. This study will test for the first time the potential of a nicotinic agonist in PD-MCI, primarily on cognitive symptoms.
Hypothesis:
The study aims to identify the most relevant cognitive areas improved by AZD0328, a selective nicotinic receptor agonist, and the underlying mechanisms involved. The study will assess magnetic resonance imaging (MRI) imaging biomarkers, to discover potential predictors of response to AZD0328, and markers of target involvement and disease progression.
Study Design:
The study is a multi-center, randomized, double-blind, placebo-controlled, Phase II study of AZD0328 in PD-MCI. The study will be conducted at sites across Europe. In the trial, 160 people 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, rating scales and a set of online cognitive tasks at the study center at baseline (day 0) and study exit (week 12). Ninety participants will also have an MRI scan at both visits, to compare brain scans obtained before and at end of treatment.
Impact on Diagnosis/Treatment of 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.
Next Steps for Development:
Being a Phase IIa study, this 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.