Neuroimaging GABA Physiology in Fragile X Syndrome

Phase 1

Terminated

• Conditions: Fragile X Syndrome (FXS); Idiopathic Intellectual Developmental Disorder (IDD)
• Interventions: Drug: [18F]flumazenil

• Registration Number: NCT04308954
• Lead Sponsor: Stanford University

Brief Summary

The investigators wish to compare the brain distribution of GABA(A) receptors and GABA levels in young adult males with Fragile X Syndrome compared to idiopathic intellectual developmental disorder. The radiopharmaceutical \[18F\]flumazenil has been used to study GABA(A) receptor distribution in other genetic syndromes with autistic features; however, despite overwhelming evidence supporting the importance of the GABAergic system in FXS, no clinical investigation of this system in human FXS has been reported in the literature. Therefore, this study will provide the first in vivo comprehensive examination of the GABAergic system in FXS using hybrid positron emission tomography/ magnetic resonance imaging (PET/MRI).

Detailed Description

Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). Converging evidence suggests that GABAergic dysfunction occurs in FXS. The investigators wish to examine brain distribution of GABA (A) receptors in young adult males with FXS using hybrid PET/MRI with \[18F\]flumazenil. This project will study the distribution of GABA(A) receptors in 15 young male adults with FXS (18-30 years old) compared to 15 age-matched male subjects with idiopathic intellectual developmental disorder (IDD) as controls. Simultaneous PET/MRI acquisition is an optimal technique to study in vivo GABAergic dysfunction and GABAa receptor distribution.

Study Timeline

• Study Start: 2016-11-01
• Primary Completion: 2018-12-06
• Study Completion: 2018-12-06
• Study First Submitted: 2020-03-11
• Study First Submitted QC: 2020-03-11
• Study First Posted: 2020-03-16
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-25
• Last Update Posted: 2021-01-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 17

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fragile X Syndrome	[18F]flumazenil	Adult males aged 18-30 years diagnosed with FXS will undergo a non-invasive F18 FMZ PET/MRI scan to determine GABA(A) receptor density; developmental dynamics of GABA(A) receptor distribution, and structural neuroanatomy and connectional anatomy.
Idiopathic Intellectual Developmental Disorder	[18F]flumazenil	Adult males aged 18-30 years diagnosed with idiopathic intellectual developmental disorder will undergo a non-invasive F18 FMZ PET/MRI scan to determine GABA(A) receptor density; developmental dynamics of GABA(A) receptor distribution, and structural neuroanatomy and connectional anatomy.

Primary Outcome Measures

Name	Time	Method
Non-displaceable binding potential of [18F]flumazenil (F18 FMZ)	Up to 2 hours per scan on a single study day	Binding potential provides an estimate of the GABA (A) receptor distribution and affinity of \[18F\]flumazenil-PET to the GABA receptors. Binding potential will be measured in patients with fragile X syndrome and control group comprising individuals with idiopathic intellectual developmental disorder.; Using imaging data obtained from PET that was corrected for attenuation and partial volume effects by MRI, nuclear medicine physicians will draw regions of interest (ROI's) around the areas of the brain listed below to estimate the F18 FMZ non-displaceable binding potential (BPnd) of F18 FMZ to GABA (A) receptors in FXS.
GABA (A) receptor density in fragile X syndrome (FXS) patients relative to control group comprising individuals with idiopathic Intellectual Developmental Disorder (IDD)	Up to 2 hours per scan on a single study day	Binding potential measurements will be compared between participants with fragile X syndrome and control group with idiopathic intellectual developmental disorder(IDD) using the PET radiotracer \[18F\]flumazenil-PET.; 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.; PET scans of FXS patients will be compared to the PET scans of control group.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States