Early Longitudinal Imaging in the Parkinson's Progressive Marker Initiative (PPMI) Using (18F)AV-133 (PPMI AV-133 Prodromal Imaging)

Early Longitudinal Imaging in the Parkinson's Progression Markers Initiative Using [18F] AV-133 (PPMI AV-133 Prodromal Imaging)

The study is a longitudinal, multi-center study to assess progression of [18F] AV-133 imaging in Prodromal PD participants. Participants will be followed for up to 24 months. Approximately 100 Prodromal participants will be recruited from up to 10 sites. Participants will be comprehensively assessed at baseline and follow up. Participants will undergo imaging assessments with [18F] AV-133 and clinical (motor, neuropsychiatric, cognitive and imaging and biomarker) assessments (conducted under the PPMI Clinical protocol).

Study Overview

• Status: Recruiting
• Conditions: Prodromal Parkinsons Disease
• Intervention / Treatment: Drug: [18F] AV-133 PET Imaging

Detailed Description

The Parkinson's Progression Marker Initiative (PPMI) is an observational, international, multi-center study designed to identify PD progression biomarkers both to improve understanding of disease etiology and course and to provide the necessary tools to enhance the likelihood of success of therapeutics studies to slow PD progression (ClinicalTrials.gov Identifier: NCT01141023). A key focus of PPMI is to identify biomarkers during the period when PD neurodegeneration is already present, but symptoms of PD have not yet occurred. This prodromal cohort would enable us to investigate PD biomarker signatures prior to onset of typical symptoms of PD. The study is a longitudinal, multi-center study to assess progression of [18F]AV-133 imaging in Prodromal PD participants. The PPMI 015 study will enroll participants from the PPMI Clinical (002) study. Participants will be followed annually for up to 24 months.

Approximately 100 Prodromal participants will be recruited from up to 10 sites. Participants will be comprehensively assessed at baseline and follow up.

Participants will undergo [18F]AV-133 PET imaging targeting the vesicular monoamine transporter. All participants will undergo an initial [18F]AV-133 PET imaging scan at baseline with repeat imaging at 12 months and 24 months.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lianne Ramia; Phone Number: 203-590-5600; Email: LRamia1@indd.org
• Study Contact Backup: Name: Jessica Dimos; Phone Number: 203-590-5600; Email: jdimos@indd.org

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T2S8
      • Not yet recruiting
      • Toronto Western Hospital
      • Contact: PPMI Call Center; Phone Number: 877-525-7764
      • Principal Investigator: Connie Marras
• Germany
  • Hessen, Germany, 35043
    • Not yet recruiting
    • Philipps-University of Marburg
    • Contact: Elisabeth Sittig; Email: sittig@med.uni-marburg.de
    • Principal Investigator: Wolfgang Oertel
• Israel
  • Tel Aviv, Israel, 64239
    • Not yet recruiting
    • Tel Aviv Sourasky Medical Center
    • Principal Investigator: Roy Alcalay, MD
    • Contact: Anat Mirelman; Phone Number: Bsc972-3-697-3014; Email: anatmi@tlvmc.gov.il
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GC
      • Not yet recruiting
      • Radboud University
      • Contact: Yara Krasowski; Email: info@onderzoek-parkinson.nl
      • Principal Investigator: Bastiaan Bloem, MD
• United Kingdom
  • Britain
    • London, Britain, United Kingdom, EC1M 6BQ
      • Recruiting
      • Queen Mary University of London
      • Contact: Cristina Simonet; Phone Number: 44-02078823379; Email: c.simonet@qmul.ac.uk
      • Principal Investigator: Cristina Simonet, MD
      • Principal Investigator: Alastair Noyce, MD
  • Tyne and Wear
    • Newcastle upon Tyne, Tyne and Wear, United Kingdom, NE45PL
      • Recruiting
      • Newcastle University
      • Principal Investigator: Nicola Pavese
      • Contact: Victoria Foster; Phone Number: +441912081197; Email: victoria.foster@ncl.ac.uk
      • Sub-Investigator: David Ledingham
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Institute for Neurodegenerative Disorders
      • Principal Investigator: Neha Prakash, MBBS
      • Contact: Mackenzee George Clinical Research Coordinator II; Phone Number: 475-318-8248; Email: mgeorge@xingimaging.com
      • Contact: Amy Ruimerman Lead Clinical Research Nurse, LPN; Phone Number: 475-318-8208; Email: aruimerman@xingimaging.com
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • University of Pennsylvania
      • Contact: PPMI Call Center; Phone Number: 877-525-7764
      • Principal Investigator: Nabila Dahodwala, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. A Prodromal PD participant, over the age of 18, confirmed as eligible to proceed to PPMI Clinical Baseline visit.
2. Able to provide informed consent.

3. Male or Female (females must meet additional criteria specified below as applicable)

   • Females must be of non-childbearing potential or using a highly effective method of birth control 14 days prior to until at least 24 hours after injection of 18F-AV-133

     • Non-childbearing potential is defined as a female that must be either postmenopausal (no menses for at least 12 months prior to PET scan) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy).
     • Highly effective method of birth control is defined as practicing at least one of the following: A birth control method that results in a less than 1% per year failure rate when used consistently and correctly, such as oral contraceptives for at least 3 months prior to injection, an intrauterine device (IUD) for at least 2 months prior to injection, or barrier methods, e.g., diaphragm or combination condom and spermicide. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.

   • Females of childbearing potential must not be pregnant, breastfeeding or lactating.

     • Includes a negative urine pregnancy test prior to injection of 18F-AV-133 on day of PET scan.

Exclusion Criteria:

1. Received any of the following medications that might interfere with 18F- AV-133 PET imaging: tetrabenazine (TBZ) or methylphenidate, reserpine, or amphetamine derivative, within 1 month prior to the Baseline 18F-AV-133 injection.
2. Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prodromal Parkinson's disease (PD); Prodromal Parkinson's disease participants enrolled in the PPMI Clinical 002 study will receive 3 injections of [18F] AV-133 and imaging procedures over the course of 24 months.	Drug: [18F] AV-133 PET Imaging; Prodromal PD participants from the PPMI Clinical (002) study will be followed for up to 24 months. These participants will undergo imaging assessments with [18F]AV-133 under this protocol at baseline, 12-month and 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F]AV-133 mean rate of change and variability	The mean rates of change and the variability around the mean of [18F]AV-133 PET SUVr in Prodromal PD patients, and where appropriate the comparison of these rates between patient subsets at study intervals ranging from 12 months to 24 months.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F]AV-133 prediction of clinical motor progression	Predictive value of [18F]AV-133 imaging Standardized Uptake Value ratio [SUVr] at baseline for longitudinal clinical progression, defined as change in Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), scale [0-260]	24 months
[18F]AV-133 prediction of clinical cognitive progression	Predictive value of [18F]AV-133 imaging Standardized Uptake Value ratio [SUVr] at baseline for longitudinal cognitive progression, defined as change in cognitive scales Montreal Cognitive Assessment (MoCA), scale [0-30]	24 months
[18F]AV133 cutoff for clinical PD	Determine [18F]AV-133 SUVr cutoff value for predicting development of clinical diagnosis of PD in people with Prodromal PD. Compare [18F]AV-133 SUVr with DaTscan SBR cutoffs for predicting the development of clinical diagnosis of PD in people with Prodromal PD.	24 months
[18F] AV133 correlation with DaTscan	Correlation between the longitudinal change of [18F]AV-133 and DaTscan.	24 months
Correlation of [18F]AV133 change with change in clinical and biomarker outcomes	Correlation between the longitudinal change of imaging outcomes and MDS-UPDRS, other clinical and blood biomarkers and sensor outcomes.	24 months
Incidence of Treatment emergent adverse events	Number of participants with treatment-related adverse events	24 months

Collaborators and Investigators

• Sponsor: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Ken Marek, MD, Institute for Neurodegenerative Disorders

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 12, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: PPMI 015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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