Clinical trial NCT04699747: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: Demyelination
Brain imaging
Positron Emission Tomography
Radiopharmaceutical
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2021-01-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Drug: F-18 3F4AP PET scan
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects
timeFrame: Baseline
measure: Number of participants with adverse events related to tracer administration as assessed by CTCAE v4.0
timeFrame: 5 years
Secondary outcomes:
measure: Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects
timeFrame: Baseline
measure: Within-subject variability in healthy controls and multiple sclerosis subjects
timeFrame: Retest within 3 months of baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: