Neuroimaging GABA Physiology in Fragile X Syndrome

NCT ID: NCT04308954

Last Updated: 2021-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2018-12-06

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.

Conditions

Fragile X Syndrome (FXS); Idiopathic Intellectual Developmental Disorder (IDD)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

[18F]flumazenil

Intervention Type: DRUG

\[18F\]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.

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.

Group Type: EXPERIMENTAL

[18F]flumazenil

Intervention Type: DRUG

\[18F\]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.

Interventions

[18F]flumazenil

\[18F\]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.

Intervention Type: DRUG

Other Intervention Names

F18 FMZ

Eligibility Criteria

Inclusion Criteria

1. Have an established diagnosis of FXS (full mutation with aberrant FMR1 methylation) by genetic testing

2. Diagnosis of intellectual disability

3. Males who are physically healthy

4. Age 18 to 30 years inclusive

5. IQ between 40 and 80 points

6. Ability to remain seated for more than 10 minutes

7. Ability to travel to Stanford

1. Age 18 to 30 years inclusive

2. Adults who are physically healthy

3. No significant recent changes in psychosocial stressors per history

4. Diagnosis of intellectual disability

5. IQ between 40 and 80 points

6. Ability to remain seated for more than 10 minutes

7. Ability to travel to Stanford

Exclusion Criteria

1. Diagnosis of a known genetic disorder (other than FXS).

2. Active medical problems such as unstable seizures, congenital heart disease, endocrine disorders.

3. Significant sensory impairments such as blindness or deafness.

4. DSM-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia.

5. Pre-term birth (<34 weeks' gestation) or low birth weight (<2000g).

6. Current use of benzodiazepines.

7. Contraindication for PET or MRI.

1. Genetic diagnosis of FXS.

2. Active medical problems such as unstable seizures, congenital heart disease, endocrine disorders.

3. Significant sensory impairments such as blindness or deafness.

4. DSM-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia.

5. Pre-term birth (<34 weeks' gestation) or low birth weight (<2000g).

6. Current use of benzodiazepines.

7. Contraindication for PET or MRI.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Frederick Chin, PhD

Assistant Professor (Research) of Radiology (General Radiology)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frederick T Chin, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

References

Lucignani G, Panzacchi A, Bosio L, Moresco RM, Ravasi L, Coppa I, Chiumello G, Frey K, Koeppe R, Fazio F. GABA A receptor abnormalities in Prader-Willi syndrome assessed with positron emission tomography and [11C]flumazenil. Neuroimage. 2004 May;22(1):22-8. doi: 10.1016/j.neuroimage.2003.10.050.

Reference Type: BACKGROUND

PMID: 15109994 (View on PubMed)

Holopainen IE, Metsahonkala EL, Kokkonen H, Parkkola RK, Manner TE, Nagren K, Korpi ER. Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABA(A) receptor beta3 subunit deletions. Ann Neurol. 2001 Jan;49(1):110-3. doi: 10.1002/1531-8249(200101)49:13.0.co;2-t.

Reference Type: BACKGROUND

PMID: 11198279 (View on PubMed)

Other Identifiers

IRB 32149

Identifier Type: -

Identifier Source: org_study_id