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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Mild Cognitive Impairment; Memory Impairment
• Intervention / Treatment: Drug: Levetiracetam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Recruiting
      • University of Queensland Centre for Clinical Research
      • Contact: Dana Pourzinal, BSc; Phone Number: 0733465028; Email: pd.research@uq.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm; 125mg Levetiracetam capsules taken twice daily (morning and evening) for 14 days	Drug: Levetiracetam; 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.
Placebo Comparator: Placebo arm; 125mg maize starch-based placebo capsules taken twice daily (morning and evening) for 14 days	Drug: Placebo; Placebo intervention will be maize-starch filled capsules with identical physical features to the active capsules.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Queensland
• Collaborators: Johns Hopkins University; Royal Brisbane and Women's Hospital; Queensland University of Technology; Cleveland Clinic Lou Ruvo Center for Brain Health

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: HREC/2020/QRBW/69379

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No