Uncovering a Novel Therapeutic Target to Reduce Dementia Risk in Parkinson's Disease

Study Overview
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Brief Summary
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The present study is a proof-of-concept clinical trial to test the efficacy of low doses of a repurposed anti-epileptic drug (levetiracetam) in treating memory problems in Parkinson's disease (PD). Neuroimaging techniques will be used to determine the effect of the drug on specific brain regions (hippocampal subfields). Finally, baseline brain activity of PD patients with memory problems will be compared to PD patients without memory problems and healthy older adults to determine if activity in specific brain regions (hippocampal subfields) can be used to predict memory problems in PD. This information will be useful for future clinical trials to target drugs to these brain regions.

Official Title
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Double-blind Randomised-controlled Within-subject Crossover Trial to Determine Levetiracetam Efficacy for Memory Impairment in Parkinson's Disease: A Proof-of-concept Study

Conditions
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Parkinson Disease, Mild Cognitive Impairment, Memory Impairment

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's Disease patients with amnestic Mild Cognitive Impairment Parkinson's Disease patients with no memory impairment Healthy volunteers All participants must be eligible to take MRI scans Exclusion Criteria: Dementia Contraindication to having MRI Bipolar disorder, Schizophrenia, Alcohol or substance abuse Major depression Suicidal Ideation Difficulty complying with protocol requirements Significant non-PD neurological disease Vascular dementia Sensitivity to levetiracetam Use of anticonvulsant medications Use of other excluded medications Severe renal impairment Clinically significant abnormalities in B12 or thyroid function test (below normative range for elderly) Females of childbearing potential
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind randomised-controlled within-subject crossover trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active arm<br>125mg Levetiracetam capsules taken twice daily (morning and evening) for 14 days | Drug: Levetiracetam<br>* Levetiracetam is currently approved in Australia and the U.S.A. for epilepsy. We will be providing levetiracetam in capsule form, 125mg levetiracetam in each capsule.<br>|
| Placebo Comparator: Placebo arm<br>125mg maize starch-based placebo capsules taken twice daily (morning and evening) for 14 days | Drug: Placebo<br>* Placebo intervention will be maize-starch filled capsules with identical physical features to the active capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pattern separation performance (behavioural outcome) | Participants' behavioural performance on the pattern separation fMRI paradigm, as measured by their proportionate accuracy of identifying the critical lure trials. | Immediately after 2 weeks of treatment | 
| Hippocampal DG/CA3 subfield activity | Participants' brain activation during the pattern separation fMRI paradigm, as measured by their activation in the critical dentate gyrus (DG)/CA3 subfield of the hippocampus during the critical lure trials of the pattern separation task. | Immediately after 2 weeks of treatment |