[18F]MC225-PET in Neurodegenerative Disease

Evaluation of [18F]MC225-PET to Measure P-glycoprotein Function in Neurodegenerative Disease

P-glycoprotein, an efflux transporter at the blood-brain barrier plays an important role in de development of neurodegenerative disease. A novel PET tracer ([18F]MC225) was developed to measure the function of P-glycoprotein and was tested with succes in healthy volunteers. This study aims to evaluate [18F]MC225 in neurodegenerative disease.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Neurodegenerative Diseases; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Drug: [18F]MC225

Detailed Description

A decrease in P-glycoprotein (P-gp) function is associated with the onset of neurodegenerative disease. New treatment strategies in neurodegenerative disease, including Parkinson's disease and Alzheimer's disease, aim to restore the P-gp function. To evaluate the effect of these potential therapies, measurement of the P-gp function is necessary. Up until now [11C]verapamil is considered to be the gold standard to measure P-gp function. However tracer uptake in the brain of [11C]verapamil is too low for adequate measurement of treatment effect, especially of restoring P-gp function. A novel PET tracer to measure P-gp function, [18F]MC225, has the potential advantage of higher brain uptake values at baseline and might therefore able to measure both up- and down regulation P-gp function. [18F]MC225 was recently studied in healthy volunteers and a method to quantify P-gp function was developed. This study aims to evaluate [18F]MC225 to measure P-gp function in neurodegenerative disease.

To this aim 10 MCI patients, 10 patients with Alzheimer's disease and 10 Parkinson's disease patients will be included and undergo one 60 min dynamic [18F]MC225 PET scan, combined with a 10 min [15O]H2O PET. Tracer uptake values (Vt) and influx (K1) in several brain regions of interest, representing local P-gp function will be compared with the [18F]MC225 uptake values in the brain of healthy volunteers obtained in a previous study.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pascalle Mossel, Msc; Phone Number: +31503616161; Email: p.mossel@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Pascalle Mossel, Msc; Phone Number: 0503616161; Email: p.mossel@umcg.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient is diagnosed with Alzheimer's disease, Parkinson's disease or Mild Cognitive Impairment

Exclusion Criteria:

• Use of any medication influencing the P-glycoprotein function
• History of neuropsychiatric disorders
• Contra-indications MRI
• Allergy contrast agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alzheimer's disease; Patients diagnosed with Alzheimer's disease	Drug: [18F]MC225; All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.
Active Comparator: Mild Cognitive Impairment; Patients diagnosed with Mild Cognitive Impairment	Drug: [18F]MC225; All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.
Active Comparator: Parkinson's disease; Patients diagnosed with Parkinson's disease	Drug: [18F]MC225; All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P-glycoprotein function	The function of P-glycoprotein at the blood-brain barrier measured by PET tracer-uptake (volume of distribution) in the brain	60 minutes

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Gert Luurtsema, Phd, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: PET; [18F]MC225; pharmacokinetic modeling
• 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; Dementia; Tauopathies; Cognition Disorders; Parkinson Disease; Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases
• Other Study ID Numbers: 202100647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No