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

NCT04699747 · Massachusetts General Hospital
In plain English

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About this study
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.
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.
Study design
Enrollment target: 60 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2021-03-25
Estimated completion: 2026-11-30
Last updated: 2025-02-27
Interventions
Drug: F-18 3F4AP
Primary outcomes
  • Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects (Baseline)
  • Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0 (5 years)
Sponsor
Massachusetts General Hospital · other
Contacts & investigators
ContactPedro Brugarolas, PhD · contact · pbrugarolas@mgh.harvard.edu · (617) 643-4574
All locations (1)
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects · TrialPath