Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects

Our overall objective is to obtain an initial assessment of the potential value of using [18F]3F4AP for imaging demyelinating diseases such as multiple sclerosis:

• Aim 1) Assess the safety of [18F]3F4AP in healthy volunteers and subjects with multiple sclerosis (MS). Hypothesis 1: Administration of [18F]3F4AP will result in no changes in vitals or other adverse events.
• Aim 2) Assess the pharmacokinetics of a bolus infusion of [18F]3F4AP in humans including healthy volunteers and MS patients. Hypothesis 2: the pharmacokinetics of [18F]3F4AP at the whole brain level will be similar in controls and MS subjects. The kinetics in demyelinated lesions will be slower than in healthy control areas.
• Aim 3) Assess the reproducibility of [18F]3F4AP in humans. Hypothesis 3: the test/retest variability of [18F]3F4AP within the same subject will be lower than 10%.
• Aim 4) Correlate MR brain images with [18F]3F4AP PET brain 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 MS. Hypothesis 5: increased PET signal (VT or SUV) will correlate with impaired Single Digit Modality Test (SDMT) scores.
• Aim 6) Correlate [18F]3F4AP PET signal with EDSS score in people with MS. Hypothesis 6: increased PET signal (VT or SUV) will correlate with higher EDSS scores.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: F-18 3F4AP

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pedro Brugarolas, PhD; Phone Number: (617) 643-4574; Email: pbrugarolas@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Pedro Brugarolas, PhD; Phone Number: 617-643-4574

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects must be ≥18 and <65 years of age;
• Able to understand and provide informed consent prior to study procedures

Exclusion Criteria:

• Subjects with known structural brain disease (e.g. brain tumor or stroke);

• Any contraindication to MRI and/or PET, including:

  • Subjects with life vest;
  • Subjects with implanted heart device (e.g. ICD, Pacemaker);
  • Subjects with metallic fragment or foreign body;
  • Subjects with other form of devices or prosthesis that are not MRI compatible, such as insulin pump, joint replacement, hearing aid, cochlear implant, permanent contraceptive devices, etc.;
  • Subjects with severe claustrophobia
  • Relative or absolute contraindication to Dotarem contrast:
• history of renal disease including acute or chronic severe renal insufficiency (glomerular filtration rate <60 mL/min/1.73m2);
• history of diabetes mellitus, systemic lupus, multiple myeloma, nephrogenic systemic fibrosis, and other co-morbidities;
• History of hypersensitive reactions to Dotarem and/or gadolinium contrast agent;
• Radiation exposure exceeds current Radiology Department guidelines (i.e., 50 mSv in the prior 12 months);
• Female subjects only: Positive serum pregnancy test, or lactating, or possibility of pregnancy cannot be ruled out prior to dosing;
• Inability to provide written informed consent;
• Any clinically significant acute or unstable physical or psychiatric condition, judged by the investigators based on medical history or screening physical examination, to be incompatible with the study;
• Any physical or psychiatric condition judged by the investigators to be incompatible with the study, based on medical history or screening physical examination;
• Abnormal results on blood tests judged by the investigators to be incompatible with the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple sclerosis; F-18 3F4AP PET Scan	Drug: F-18 3F4AP; Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).; Other Names: [18F]3F4AP
Active Comparator: Healthy controls; F-18 3F4AP PET Scan	Drug: F-18 3F4AP; Subjects will be injected once per imaging session (a maximum of 2 imaging sessions) with up to 10 mCi (±20%) of 18-F 3F4AP as a rapid intravenous bolus (within 1 min).; Other Names: [18F]3F4AP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects	Binding of the tracer will be quantified using volumes of distribution (VTs). Volume of distribution is the ratio of tracer concentration in tissue to plasma at equilibrium and will be determined using standard pharmacokinetic methods (Innis et al, J Cereb Blood Flow Metab. 2007; 27(9): 1533-1539).	Baseline
Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0	Determine number of participants adverse events related to tracer administration as assessed by CTCAE v4.0	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects	Binding of the tracer in the lesions will be quantified using volumes of distribution (VTs). Lesions will be delineated based on 3D FLAIR MRI using standardized methods.	Baseline
Within-subject variability in healthy controls and multiple sclerosis subjects	Within-subject variability (test/retest variability or TRV) of the VT in healthy volunteers and multiple sclerosis subjects	Retest within 3 months of baseline

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; Brain imaging; Demyelination; Radiopharmaceutical
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Demyelinating Diseases
• Other Study ID Numbers: 2020P002459

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