Exploring the Utility of [18F]3F4AP for Demyelination Imaging in Controls, Neurodegeneration and Traumatic Brian Injury

The overall objective is to obtain an initial assessment of the value of using [18F]3F4AP for imaging demyelinating diseases such as traumatic brain injury (TBI), neurodegenerative diseases such as mild cognitive impairment (MCI) and Alzheimer's Disease (AD):

• Aim 1) Assess the safety of [18F]3F4AP in healthy volunteers and subjects with traumatic brain injury (TBI) and neurocognitive impaired subjects (AD/MCI). Hypothesis 1: Administration of [18F]3F4AP will result in no changes in vitals or other adverse events.
• Aim 2) Assess the radiation doses to the main organs in healthy volunteers. Hypothesis 2: the radiation doses to each organ will be comparable in all subjects and within the acceptable limits.
• Aim 3) Assess the pharmacokinetics of a bolus infusion of [18F]3F4AP in humans including healthy volunteers and patients. Hypothesis 3: the pharmacokinetics of [18F]3F4AP at the whole brain level will be similar in controls, TBI and AD/MCI subjects. The kinetics in demyelinated lesions will be slower than in healthy areas.
• Aim 4) Correlate MR images with [18F]3F4AP PET images. Hypothesis 4A: all the lesions seen on the MRI will show increased signal (VT or SUV) on the PET images. Hypothesis 4B: some of the lesions on the MRI will show increased signal (VT or SUV) on the PET but not all.
• Aim 5) Correlate [18F]3F4AP PET signal with neuropsychological testing in people with TBI and AD/MCI. Hypothesis 5A: increased PET signal (VT or SUV) will correlate with impaired Mini Mental State Examination (MMSE).

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Injuries, Traumatic; Alzheimer Disease; Demyelinating Disorder
• Intervention / Treatment: Drug: F18-3F4AP

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Marc Normandin, PhD; Phone Number: 6176436836; Email: normandin@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects are 18 years of age and older, except AD subjects who are 60 to 90 years of age.

Exclusion Criteria:

• A subject will not be eligible for inclusion in this study if any of the exclusion criteria for PET/CT or MRI studies applies. A negative STAT quantitative serum hCG pregnancy test is required on the day of the PET/CT scan before female subjects of childbearing potential can participate. Any woman of childbearing potential, who is seeking to become pregnant, is breastfeeding, or who suspects she may be pregnant will not be enrolled in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Controls	Drug: F18-3F4AP; PET Scan
Experimental: Safety/Dosimetry Cohort	Drug: F18-3F4AP; PET Scan
Experimental: Traumatic Brain Injury	Drug: F18-3F4AP; PET Scan
Experimental: AD/MCI	Drug: F18-3F4AP; PET Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Determine number of participants with treatment-related adverse events as assessed by CTCAE v4.0	5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Marc Normandin, PhD, Mass. General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: 3F4AP
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Craniocerebral Trauma; Trauma, Nervous System; Dementia; Tauopathies; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Alzheimer Disease; Demyelinating Diseases; Nerve Degeneration
• Other Study ID Numbers: 2020P002254

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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