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

NCT04643327 | Recruiting Phase 2

• 1 other identifier: HREC/2020/QRBW/69379
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Mild Cognitive Impairment; Memory Impairment

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Active arm

EXPERIMENTAL

125mg Levetiracetam capsules taken twice daily (morning and evening) for 14 days

Drug: Levetiracetam

Placebo arm

PLACEBO COMPARATOR

125mg maize starch-based placebo capsules taken twice daily (morning and evening) for 14 days

Drug: Placebo

Interventions

Levetiracetam DRUG

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.

Active arm

Placebo DRUG

Placebo intervention will be maize-starch filled capsules with identical physical features to the active capsules.

Placebo arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University of Queensland Centre for Clinical Research

Brisbane, Queensland, 4029, Australia

RECRUITING

Related Publications (1)

• Dissanayaka N, Pourzinal D, Byrne GJ, Yang J, McMahon KL, Pontone GM, O'Sullivan JD, Adam R, Littleford R, Chatfield M, Lehn A, Mari Z, Bakker A. Levetiracetam for the treatment of mild cognitive impairment in Parkinson's disease: a double-blind controlled proof-of-concept trial protocol. Pilot Feasibility Stud. 2023 Nov 22;9(1):189. doi: 10.1186/s40814-023-01406-y.

  PMID: 37993889 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction; Memory Disorders

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: NHMRC Boosting Dementia Research Leadership Fellow

Model Details: Double-blind randomised-controlled within-subject crossover trial

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 25, 2020
• Study Start: February 9, 2021
• Primary Completion: January 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Locations

AU (1)