Novel Clinical Target in Fragile X Syndrome

NCT04314856 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IRB 50016
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Fragile X Syndrome (FXS)

Keywords

FXS

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Study Arms (2)

Fragile X Syndrome

EXPERIMENTAL

Adult 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.

Drug: 18F-FTC-146

Healthy Volunteers (Control)

EXPERIMENTAL

Adults 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.

Drug: 18F-FTC-146

Interventions

18F-FTC-146 DRUG

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

Also known as: FTC146

Fragile X Syndrome; Healthy Volunteers (Control)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: For FXS only: Participants must be male adults between 18 and 30 years with Fragile X-syndrome
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Guido A. Davidzon, MD, SM: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (3)

• 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.

  PMID: 30349360 BACKGROUND

• 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.

  PMID: 28280965 BACKGROUND

• 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.

  PMID: 28572487 BACKGROUND

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Study Officials

• Guido Davidzon, MD SM

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Radiology/Nuclear Medicine & Molecular Imaging

Model Details: 15 male subjects with FXS will be compared to 5 healthy volunteers who will be the control group.

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 19, 2020
• Study Start: January 12, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)