Fragile X Syndrome (FXS)Phase 1NCT04308954

Neuroimaging GABA Physiology in Fragile X Syndrome

A Phase 1 study testing [18F]flumazenil in people with Fragile X Syndrome (FXS) and Idiopathic Intellectual Developmental Disorder (IDD), run by Stanford University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 30 years, men only
Conditions the study is for: Fragile X Syndrome (FXS), Idiopathic Intellectual Developmental Disorder (IDD)
What is being tested?: [18F]flumazenil
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteUnited States
Study dates: 1 Nov 2016to 6 Dec 2018
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 30 years
Men only
No healthy volunteers
Adult

Who may be able to join

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

Show all 14Show fewer

Ability to travel to Stanford
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

Who cannot join

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.

Show all 14Show fewer

Contraindication for PET or MRI.
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.

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: Cross-Species Multi-Modal Neuroimaging to Investigate GABA Physiology in Fragile X Syndrome

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).

Read the 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)
Being tested: [18F]flumazenil
Keywords: FXS, Intellectual Disability
Medical subject headings: Fragile X Syndrome, Intellectual Disability

What participants receive

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

[18F]flumazenilDrug
Also called F18 FMZ
[18F]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.

Study groups in NCT04308954
Study group	Role	What they receive
Fragile X Syndrome	Experimental	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. Receives: Drug: [18F]flumazenil
Idiopathic Intellectual Developmental Disorder	Experimental	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. Receives: Drug: [18F]flumazenil

What is being measured

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

Non-displaceable binding potential of [18F]flumazenil (F18 FMZ)
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.
Measured: Up to 2 hours per scan on a single study day
GABA (A) receptor density in fragile X syndrome (FXS) patients relative to control group comprising individuals with idiopathic Intellectual Developmental Disorder (IDD)
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.
Measured: Up to 2 hours per scan on a single study day

Timeline

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

1 Nov 20166 Dec 2018

First posted16 Mar 2020
Study start1 Nov 2016
Primary completion6 Dec 2018
Study completion6 Dec 2018

Why it stopped: Difficulty with patient recruitment due to COVID-19 pandemic

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Fragile X Syndrome (FXS)Studies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
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)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04308954
Sponsor's protocol ID: IRB 32149
Status last verified: Jan 2021
First submitted: 11 Mar 2020
Last updated: 28 Jan 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 15109994
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.
PubMed 11198279

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Fragile X Syndrome (FXS) trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cross-Species Multi-Modal Neuroimaging to Investigate GABA Physiology in Fragile X Syndrome
ClinicalTrials.gov ID: NCT04308954
Acronym / sponsor ID: IRB 32149
Conditions: Fragile X Syndrome (FXS), Idiopathic Intellectual Developmental Disorder (IDD)
Keywords: FXS, Intellectual Disability
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Difficulty with patient recruitment due to COVID-19 pandemic
Enrolment: 17 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Study start: 1 Nov 2016 (actual)
Primary completion: 6 Dec 2018 (actual)
Study completion: 6 Dec 2018 (actual)
First posted: 16 Mar 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
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.

Arm	Type	Receives
Fragile X Syndrome	Experimental	Drug: [18F]flumazenilAdult 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	Experimental	Drug: [18F]flumazenilAdult 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.

Who may qualify

Ages: 18 to 30 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (14 listed)

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

Key exclusion criteria (14 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
[18F]flumazenilAlso: F18 FMZ[18F]flumazenil is a PET radiopharmaceutical that can be used to determine gamma-aminobutyric acid (GABA(A)) receptor density.	Drug	Fragile X Syndrome, Idiopathic Intellectual Developmental Disorder

Primary outcome

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.

Results and safety

The study was stopped early (reason given: Difficulty with patient recruitment due to COVID-19 pandemic). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2021.
Background: PubMed 15109994Lucignani 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.
Background: PubMed 11198279Holopainen 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.
Individual participant dataSharing planned: No

Related trials for Fragile X Syndrome (FXS)

Not yet recruitingPhase 2
Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Frederick T Chin, PhD principal investigator

Stanford University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [18F]flumazenil in people with Fragile X Syndrome (FXS) and Idiopathic Intellectual Developmental Disorder (IDD), run by Stanford University 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 14 inclusion and 14 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: stopped early, as of the sponsor's last update on 28 Jan 2021. 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 stopped early (reason given: Difficulty with patient recruitment due to COVID-19 pandemic). Results are not available in the source record.

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?

Non-displaceable binding potential of [18F]flumazenil (F18 FMZ) (time frame: Up to 2 hours per scan on a single study day). 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 NCT04308954, which also lists 2 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 28 Jan 2021.