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Fragile X Syndrome (FXS)Phase 1NCT04314856

Novel Clinical Target in Fragile X Syndrome

A Phase 1 study testing 18F-FTC-146 in people with Fragile X Syndrome (FXS), run by Guido A. Davidzon, MD, SM at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). The investigators wish to examine brain distribution of sigma-1 receptors in young adult males with FXS using 18F-FTC-146 PET. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Fragile X Syndrome (FXS)
What is being tested?
18F-FTC-146
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
12 Jan 2021to Jun 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Ages 18-65
  • Either gender and all ethno-racial categories
  • Capacity to provide informed consent
  • Female participants are expected to use an effective method of birth control throughout the study which includes: hormonal methods (birth control pills, patches, injections, vaginal ring or implants), barrier method (condom or diaphragm) used with spermicide, intrauterine device (IUD), or abstinence (no sex)
  • Can travel to Stanford for 2 scan days.
  • Males who are physically healthy
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  • Aged between 18 and 30 years inclusive
  • Can travel to Stanford for a 2-day visit.
  • IQ between 40 and 80 points.
  • Ability to remain seated for more than 10 minutes.
  • Have an established genetic diagnosis of FXS (full mutation with evidence of aberrant methylation of the FMR1 gene, confirmed by genetic testing).

Who cannot join

  • Any current or lifetime psychiatric diagnosis
  • Current or past use of psychotropic medication for purposes of treating a mental illness
  • Pregnant or nursing females
  • Major medical or neurological problem, including anemia (Hb , 12 g/dl in women and <14 g/dl in men) (e.g., unstable hypertension, seizure disorder, head trauma)
  • Current diagnosis of vasculopathy or Raynouds
  • Participant is unable to tolerate being off of anticoagulant medication during study
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  • Positive urine screen for illicit drugs
  • Presence of metal in the body that is contraindicated for MRI scans
  • Current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits
  • Stanford University student status (i.e., we will exclude students such as undergrads, grad students and postdocs that currently attend at Stanford University)
  • Any contraindication for MRI scanning procedures (metal in body, braces, claustrophobia, etc.)
  • No history of with substance abuse, traumatic brain injury and
  • BMI greater than 18.5
  • Diagnosis of a known genetic disorder (other than FXS).
  • Active medical problems such as unstable seizures, congenital heart disease, endocrine disorders.
  • Significant sensory impairments such as blindness or deafness.
  • DSM-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia.
  • Pre-term birth (<34 weeks' gestation) or low birth weight (<2000g).
  • Current use of benzodiazepines. Individuals who are taking concomitant psychoactive medications will be tracked and examined in post-hoc analyses, given that it is extremely difficult to recruit individuals who are medication-free or who are willing to go off those medications prior to entering the study.
  • Current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Sigma-1 Receptors: A Novel Clinical Target in Fragile X Syndrome

Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). The investigators wish to examine brain distribution of sigma-1 receptors in young adult males with FXS using 18F-FTC-146 PET. This project will study the distribution of sigma-1 receptors in 15 young (18-30 years) male adults with FXS compared to 5 healthy adult volunteers.

Read the detailed description

In this study, we measured sigma-1 receptor density in the regions of interest in brain known to be involved in executive functioning and cognition using 18F-FTC-146 PET. We then compared S1R density in areas ROIs not involved in executive functioning and cognition. This provided a framework for predicting functional impairment based on brain-behavior relationships.

The study had two aims. The first aim was to evaluate the reliability of 18F-FTC-146 brain uptake in healthy controls under test and retest conditions to establish a baseline measure of S1R density and quantify regional brain uptake of radiotracer in five healthy adults. The second aim was to characterize S1R density in brains of young adult males with FXS which will then be compared to healthy volunteers.

This was the very first PET study to image sigma-1 receptor density in participants with fragile X syndrome, thereby testing whether altered receptor density is present in brain in fragile X syndrome patients when compared to healthy volunteers. If confirmed, the current study would have provided compelling clinical-translational support for an important pathophysiological mechanism of cognition and executive function. The study had considerable potential for advancing the neurobiological understanding of fragile X syndrome in humans.

Being tested
18F-FTC-146
Keywords
FXS
Medical subject headings
Fragile X Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 18F-FTC-146Drug

    Also called FTC146

    18F-FTC-146 is a PET radiopharmaceutical that can be used to determine sigma-1 receptor density.

Study groups in NCT04314856
Study groupRoleWhat they receive
Fragile X SyndromeExperimentalAdult males aged 18-30 years diagnosed with FXS will undergo a PET/MRI scan using 18F-FTC-146 to determine sigma-1 receptor density. These participants will only be administered once with 18F-FTC-146.
Receives: Drug: 18F-FTC-146
Healthy Volunteers (Control)ExperimentalAdults aged 18-65 years undergo a PET/MRI scan using 18F-FTC-146 to determine sigma-1 receptor density. Test-retest studies will be performed where these individuals will each be injected twice with 18F-FTC-146.
Receives: Drug: 18F-FTC-146

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of concordant readings of regional brain uptake of radiotracer [18F]FTC-146 as a measure of reliability under test-retest conditions

    Regional brain uptake of [18F]FTC-146 will be analyzed by kinetic modeling with metabolite-corrected arterial input functions to establish stability and reproducibility of [18F] FTC-146 in humans under test and retest conditions.

    This outcome will be assessed in healthy volunteers only.

    Measured: Up to 6 hours per scan performed on Day 0 (Test) and Day 7 (Retest)

  2. Difference in Non-displaceable Binding Potential (BPND) of [18F]FTC-146 in fragile X syndrome (FXS) patients relative to healthy volunteers

    Binding potential provides an estimate of the S1R receptor distribution and affinity of [18F]FTC-146 to the S1R receptors. Binding potential measurements will be compared between participants with fragile X syndrome and control group with healthy volunteers to assess if there is a difference. Binding Potential (BPND) is estimated as the distribution volume ratio (DVR) -1.

    DVR's of tracers are used in PET receptor studies where the radiopharmaceutical can be specifically bound to receptors; nonspecifically bound to other macromolecular components, or free in tissue (FT). DVR is calculated using a Logan Plot, which uses the dynamic PET images obtained during imaging and compartment modeling to graphically analyze by linear regression pharmacokinetic data for radiopharmaceuticals that undergo 'reversible' uptake.

    Healthy volunteers will have scans at Day 0 and Day 7, and FXS patients will have a single scan on day 0. All scans will be analyzed.

    Measured: Up to 6 hours per scan performed on Day 0 (both groups) and Day 7 (healthy volunteers)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2020
  2. Study start12 Jan 2021
  3. Primary completionJun 2022 (estimated)
  4. Study completionJun 2022 (estimated)

Why it stopped: Principal investigator left institution

Resources

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
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
15 male subjects with FXS will be compared to 5 healthy volunteers who will be the control group.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04314856
Sponsor's protocol ID
IRB 50016
Status last verified
Nov 2022
First submitted
11 Mar 2020
Last updated
15 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cipriano PW, Lee SW, Yoon D, Shen B, Tawfik VL, Curtin CM, Dragoo JL, James ML, McCurdy CR, Chin FT, Biswal S. Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report. J Pain Res. 2018 Oct 12;11:2353-2357. doi: 10.2147/JPR.S167839. eCollection 2018.

    PubMed 30349360

  • Shen B, Park JH, Hjornevik T, Cipriano PW, Yoon D, Gulaka PK, Holly D, Behera D, Avery BA, Gambhir SS, McCurdy CR, Biswal S, Chin FT. Radiosynthesis and First-In-Human PET/MRI Evaluation with Clinical-Grade [18F]FTC-146. Mol Imaging Biol. 2017 Oct;19(5):779-786. doi: 10.1007/s11307-017-1064-z.

    PubMed 28280965

  • Hjornevik T, Cipriano PW, Shen B, Park JH, Gulaka P, Holley D, Gandhi H, Yoon D, Mittra ES, Zaharchuk G, Gambhir SS, McCurdy CR, Chin FT, Biswal S. Biodistribution and Radiation Dosimetry of 18F-FTC-146 in Humans. J Nucl Med. 2017 Dec;58(12):2004-2009. doi: 10.2967/jnumed.117.192641. Epub 2017 Jun 1.

    PubMed 28572487

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 18F-FTC-146 in people with Fragile X Syndrome (FXS), run by Guido A. Davidzon, MD, SM 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 11 inclusion and 20 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: withdrawn, as of the sponsor's last update on 15 Nov 2022. 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?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of concordant readings of regional brain uptake of radiotracer [18F]FTC-146 as a measure of reliability under test-retest conditions (time frame: Up to 6 hours per scan performed on Day 0 (Test) and Day 7 (Retest)). 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 NCT04314856, which also lists 3 linked publications.

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 15 Nov 2022.

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