Somatotopy in Parkinson's Disease

NCT ID: NCT04876404

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-25
• Study Completion Date: 2024-08-01

Brief Summary

This study aims to assess changes in connections within the brain in Parkinson's disease (PD). We will invite up to 10 people with PD to participate in this study and complete several brain scans using PET (Positron Emission Tomography) and fMRI (functional Magnetic Resonance Imaging) on the Hybrid PET/MRI scanner. We will also invite 10 participants without PD to complete the same scans for comparison. "Somatotopy" refers to how areas of the brain are organized according to the body part they affect. The striatum is the brain region that coordinates complex thinking and movement. Plasticity refers to changes in connections within the brain, which can happen to make up for changes that are related to PD. In this study we will use PET and fMRI imaging together to investigate changes in the striatum in people affected by Parkinson's disease. The hybrid PET/MR scanner allows us to perform simultaneous PET and MRI measurements to investigate this.

Detailed Description

Purpose

The current investigation aims to study the altered striatal plasticity in early stage PD versus healthy controls to delineate the functional reorganization of dopaminergic projections in PD neurodegeneration. Analysis will be initially restricted to early PD, when compensatory mechanisms are likely compensating for deficits arising from dopamine deficiency. The use of hybrid PET-MRI imaging will allow for the simultaneous assessment of patterns of striatal activation and functional connectivity, as well as dopamine release induced by a variety of cognitive and motor tasks. In the future, depending upon the findings of this study, we will examine the effects of disease progression on segregation of striatal function. Altered plasticity is likely to contribute to clinical progression of disease and to disease and treatment related complications, thus this investigation may help advance the development of more effective PD treatment measures.

This investigation is intended as a pilot study. We currently do not have data on which to base a power analysis for sample size, however based on our previous experience using a double or triple bolus [11C] raclopride techniques, a sample size of 10 individuals per study group is adequate to detect between-group differences in dopamine release using a single bolus technique. Previous investigations we will be referencing in our study have similarly relied on small sample sizes to obtain their data.

We are specifically interested in tracking functional changes within the brain in early PD, as this is when compensatory mechanisms are still compensating for deficits arising from dopamine deficiency. Thus for the purposes of this investigation we would like to focus on early PD, with the potential to follow the PD cohort in a longitudinal fashion in future investigations, to assess progressive loss of segregation over time.

Hypotheses

1. In healthy subjects, there will be segregation of striatal activation as measured by cerebral blood flow determined by BOLD fMRI, as well as striatal dopamine release determined using simultaneous [11C]raclopride PET, according to body site (motor activation) and task type (motor vs. cognitive vs. reward)

2. In patients with PD, this segregation will be lost in a progressive fashion, in which caudal and dorsal striatal activation and dopamine release are lost first, with these functions shifted to progressively more rostral and ventral regions of the striatum.

Research Design

This is a cross-sectional study on 20 subjects (10 healthy control, 10 PD), involving 2-3 visits per subject to the Pacific Parkinson's Research Centre in UBC, Vancouver, BC. Each study participant will undergo 4 separate scans, 2 scans per day.

Conditions

Parkinson Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Parkinson's Disease

Individuals with early stage Parkinson's Disease (diagnosed within the last 5 years)

PET/MR Imaging

Intervention Type: DIAGNOSTIC_TEST

The hybrid PET/MR scanner can provide information on brain activity during various motor and cognitive tasks.

Healthy Controls

Healthy control individuals with no neurological or mood disorders.

PET/MR Imaging

Intervention Type: DIAGNOSTIC_TEST

The hybrid PET/MR scanner can provide information on brain activity during various motor and cognitive tasks.

Interventions

PET/MR Imaging

The hybrid PET/MR scanner can provide information on brain activity during various motor and cognitive tasks.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Positron Emission Tomography and Magnetic Resonance Imaging

Eligibility Criteria

Inclusion Criteria

i. Recently diagnosed with early stage Parkinson's Disease (within 5 years of diagnosis) ii. Between the ages of 50 to 85 iii. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Healthy Control Individuals

i. Healthy male between the ages of 50 and 85 ii. Healthy female between the ages of 50 and 85 iii. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Exclusion Criteria

i. Current or past major psychiatric disorders (e.g. depression, anxiety disorders) or other major neurological disease ii. Current or past substance use problems iii. Serious head injury with loss of consciousness for ≥ 5 minutes iv. Fear of enclosed, confined spaces v. Pregnant or breastfeeding vi. Presence of active, recent, or repeated cancer vii. Unstable/undiagnosed medical conditions viii. Certain medications or conditions may impact the ability to participate and these will be discussed on a case by case basis with the study team.

ix. Weight of more 158 kg x. Inability to remain still during the scans. xi. People for whom MRI is contra-indicated:

• People with a non-MRI safe intrauterine device (IUD);
• Machinist or Metalworkers;
• Cardiac pacemaker, wires or defibrillator;
• Past injury where a piece of metal lodged in your eye or orbit;
• Ferromagnetic aneurysm clip;
• Artificial heart valve;
• Brain aneurysm clip;
• Electrical stimulator for nerves or bones or brains;
• Ear or eye implant;
• Implanted drug infusion pump;
• Coil, catheter, or filter in any blood vessel;
• Orthopaedic hardware (artificial joint, plate, screws);
• Other metallic prostheses;
• Shrapnel, bullets, or other metal fragments;
• Surgery (brain or otherwise), tattoos or injection into a join in the last 6 weeks

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of British Columbia

OTHER

Sponsor Role: collaborator

Pacific Parkinson's Research Centre

OTHER

Sponsor Role: lead

Responsible Party

A. Jon Stoessl

Professor & Head of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jess McKenzie

Role: STUDY_DIRECTOR

Pacific Parkinson's Research Centre

Locations

UBC Pacific Parkinson's Research Centre

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H19-03166

Identifier Type: -

Identifier Source: org_study_id