search
Back to results

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

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
F-18 3F4AP
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Multiple Sclerosis focused on measuring Demyelination, Brain imaging, Positron Emission Tomography, Radiopharmaceutical

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Multiple sclerosis

Healthy controls

Arm Description

F-18 3F4AP PET Scan

F-18 3F4AP PET Scan

Outcomes

Primary Outcome Measures

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).
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

Secondary Outcome Measures

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.
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

Full Information

First Posted
December 16, 2020
Last Updated
October 19, 2023
Sponsor
Massachusetts General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04699747
Brief Title
Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects
Official Title
Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 25, 2021 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Demyelination, Brain imaging, Positron Emission Tomography, Radiopharmaceutical

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Drug: F-18 3F4AP PET scan
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Multiple sclerosis
Arm Type
Experimental
Arm Description
F-18 3F4AP PET Scan
Arm Title
Healthy controls
Arm Type
Active Comparator
Arm Description
F-18 3F4AP PET Scan
Intervention Type
Drug
Intervention Name(s)
F-18 3F4AP
Other Intervention Name(s)
[18F]3F4AP
Intervention Description
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).
Primary Outcome Measure Information:
Title
Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects
Description
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).
Time Frame
Baseline
Title
Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0
Description
Determine number of participants adverse events related to tracer administration as assessed by CTCAE v4.0
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects
Description
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.
Time Frame
Baseline
Title
Within-subject variability in healthy controls and multiple sclerosis subjects
Description
Within-subject variability (test/retest variability or TRV) of the VT in healthy volunteers and multiple sclerosis subjects
Time Frame
Retest within 3 months of baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pedro Brugarolas, PhD
Phone
(617) 643-4574
Email
pbrugarolas@mgh.harvard.edu
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pedro Brugarolas, PhD
Phone
617-643-4574

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs