Multiple SclerosisPhase 1NCT04699747
Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects
A Phase 1 study testing F-18 3F4AP in people with Multiple Sclerosis, run by Massachusetts General Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- F-18 3F4AP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2021to 30 Sep 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must be ≥18 and <65 years of age;
- Able to understand and provide informed consent prior to study procedures
Who cannot join
- 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.;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Pedro Brugarolas, PhD, 617-643-4574
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.
- Conditions
- Multiple Sclerosis
- Being tested
- F-18 3F4AP
- Keywords
- Demyelination, Brain imaging, Positron Emission Tomography, Radiopharmaceutical
- Medical subject headings
- Multiple Sclerosis, Demyelinating Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F-18 3F4APDrug
Also called [18F]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).
| Study group | Role | What they receive |
|---|---|---|
| Multiple sclerosis | Experimental | F-18 3F4AP PET Scan Receives: Drug: F-18 3F4AP |
| Healthy controls | Active comparator | F-18 3F4AP PET Scan Receives: Drug: F-18 3F4AP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Measured: 5 years
Secondary outcomes (2)
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.
Measured: 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
Measured: Retest within 3 months of baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start25 Mar 2021
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Drug: F-18 3F4AP PET scan
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pedro Brugarolas, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04699747
- Sponsor's protocol ID
- 2020P002459
- Status last verified
- Oct 2026
- First submitted
- 16 Dec 2020
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tiss A, Michaelson NM, Russo AW, Ramos-Torres KM, Sun Y, DaSilva NE, Noel JM, Liu F, Gong K, Huang SY, Popko B, Baker S, Klawiter EC, Brugarolas P. First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions. Eur J Nucl Med Mol Imaging. 2026 Jan;53(2):1125-1138. doi: 10.1007/s00259-025-07454-1. Epub 2025 Aug 5.
PubMed 40759830
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Utility of Demyelination Tracer [18F]3F4AP in Controls and Multiple Sclerosis Subjects
- ClinicalTrials.gov ID
- NCT04699747
- Acronym / sponsor ID
- 2020P002459
- Conditions
- Multiple Sclerosis
- Keywords
- Demyelination, Brain imaging, Positron Emission Tomography, Radiopharmaceutical
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 25 Mar 2021 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 7 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Drug: F-18 3F4AP PET scan
| Arm | Type | Receives |
|---|---|---|
| Multiple sclerosis | Experimental | Drug: F-18 3F4APF-18 3F4AP PET Scan |
| Healthy controls | Active comparator | Drug: F-18 3F4APF-18 3F4AP PET Scan |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects must be ≥18 and <65 years of age;
- Able to understand and provide informed consent prior to study procedures
Key exclusion criteria (17 listed)
- Subjects with known structural brain disease (e.g. brain tumor or stroke);
- Any contraindication to MRI and/or PET, including:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| F-18 3F4APAlso: [18F]3F4APSubjects 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). | Drug | Healthy controls, Multiple sclerosis |
Primary outcome
Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects
Time frame: Baseline
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
Time frame: 5 years
Determine number of participants adverse events related to tracer administration as assessed by CTCAE v4.0
2 secondary outcomes
Binding of 18-F 3F4AP in brain lesions of multiple sclerosis subjects
Time frame: Baseline
Within-subject variability in healthy controls and multiple sclerosis subjects
Time frame: Retest within 3 months of baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Results publication: PubMed 40759830Tiss A, Michaelson NM, Russo AW, Ramos-Torres KM, Sun Y, DaSilva NE, Noel JM, Liu F, Gong K, Huang SY, Popko B, Baker S, Klawiter EC, Brugarolas P. First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions. Eur J Nucl Med Mol Imaging. 2026 Jan;53(2):1125-1138. doi: 10.1007/s00259-025-07454-1. Epub 2025 Aug 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing F-18 3F4AP in people with Multiple Sclerosis, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pedro Brugarolas, PhD ((617) 643-4574, pbrugarolas@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Binding of 18-F 3F4AP in the brain of healthy volunteers and multiple sclerosis subjects (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04699747, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.