Neuroimaging GABA Physiology in Fragile X Syndrome
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04308954 |
Recruitment Status :
Terminated
(Difficulty with patient recruitment due to COVID-19 pandemic)
First Posted : March 16, 2020
Last Update Posted : January 28, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Fragile X Syndrome (FXS) Idiopathic Intellectual Developmental Disorder (IDD) | Drug: [18F]flumazenil | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 17 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | 15 male subjects with FXS will be compared to 15 subjects with idiopathic intellectual developmental disorder, who will be the control group. Young male adults with idiopathic intellectual developmental disorder will be (group) matched to FXS participants for mean age (and age range), handedness, socioeconomic status and ethnicity. |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | Cross-Species Multi-Modal Neuroimaging to Investigate GABA Physiology in Fragile X Syndrome |
Actual Study Start Date : | November 1, 2016 |
Actual Primary Completion Date : | December 6, 2018 |
Actual Study Completion Date : | December 6, 2018 |

Arm | Intervention/treatment |
---|---|
Experimental: Fragile X Syndrome
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.
|
Drug: [18F]flumazenil
[18F]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.
Other Name: F18 FMZ |
Experimental: Idiopathic Intellectual Developmental Disorder
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.
|
Drug: [18F]flumazenil
[18F]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.
Other Name: F18 FMZ |
- Non-displaceable binding potential of [18F]flumazenil (F18 FMZ) [ Time Frame: 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) [ Time Frame: 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 30 Years (Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | Participants must be male adults with idiopathic intellectual developmental disorder (IDD) or fragile X-syndrome (FXS) |
Accepts Healthy Volunteers: | No |
Inclusion Criteria for participants with FXS:
- Have an established diagnosis of FXS (full mutation with aberrant FMR1 methylation) by genetic testing
- Diagnosis of intellectual disability
- Males who are physically healthy
- Age 18 to 30 years inclusive
- IQ between 40 and 80 points
- Ability to remain seated for more than 10 minutes
- Ability to travel to Stanford
Exclusion criteria for participants with FXS:
- 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.
- Contraindication for PET or MRI.
Inclusion criteria for participants with IDD:
- Age 18 to 30 years inclusive
- Adults who are physically healthy
- No significant recent changes in psychosocial stressors per history
- Diagnosis of intellectual disability
- IQ between 40 and 80 points
- Ability to remain seated for more than 10 minutes
- Ability to travel to Stanford
Exclusion Criteria for participants with IDD:
- Genetic diagnosis of 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.
- Contraindication for PET or MRI.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04308954
United States, California | |
Stanford University | |
Stanford, California, United States, 94305 |
Principal Investigator: | Frederick T Chin, PhD | Stanford University |
Responsible Party: | Frederick Chin, PhD, Assistant Professor (Research) of Radiology (General Radiology), Stanford University |
ClinicalTrials.gov Identifier: | NCT04308954 |
Other Study ID Numbers: |
IRB 32149 |
First Posted: | March 16, 2020 Key Record Dates |
Last Update Posted: | January 28, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
FXS, Intellectual Disability |
Fragile X Syndrome Intellectual Disability Syndrome Developmental Disabilities Disease Pathologic Processes Mental Retardation, X-Linked Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Sex Chromosome Disorders Chromosome Disorders Congenital Abnormalities |
Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Neurodevelopmental Disorders Mental Disorders Flumazenil Antidotes Protective Agents Physiological Effects of Drugs GABA Modulators GABA Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |