Fragile X SyndromeNCT06293027
Optical Imaging as a Tool for Monitoring Brain Function in Fragile X Syndrome
An observational study of Fragile X Syndrome, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
Trial summary
The objective of this project is to explore the potential of functional near- infrared spectroscopy (fNIRS) as innovative functional biomarker for clinical trial readiness in Fragile X Syndrome (FXS) that is still without cure. Read more about this study
- Who is it for?
- Ages 2 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Fragile X Syndrome
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2023to 15 Dec 2025
- Phase
- Observational
- 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 2 years and older
- Men only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Fragile X syndrome (FXS) is the most commonly inherited form of mental retardation and developmental disabilities, affecting 1 in 4000 individuals. The phenotype of FXS involves mental retardation or learning disabilities, social deficit, anxiety, attention deficit, impulsivity, hyperarousal, mood instability, inflexibility, prominent ears, long face, and hyperextensible finger joints. There is no effective treatment for FXS, and the standard of care include therapies that help minimise the symptoms of the condition.
Who may be able to join
- FXS participants:
- Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment
- Diagnosed with FXS with a previously identified pathogenic or likely pathogenic variant in the FMR1 gene.
- Must also meet the diagnostic criteria for FXS.
- Male
- Typically developing participants:
Show all 10Show fewer
- Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment
- Age- and sex-matched to the FXS participants
- No underlying genetic diagnosis or past/chronic medical condition associated with increased risk for autism spectrum disorder (ASD) and/or ID
- Typical neurodevelopment for age (no established diagnosis or clinical suspicion for ASD or ID)
Who cannot join
- For FXS and Typically developing participants:
- Unwilling or unable to comply with study procedures and assessments
- Contraindications to fNIRS, such as uncooperative or destructive behaviors preventing lead placement or capture by fNIRS equipment
- Traumatic loss of consciousness in the last year
- Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
- If participant is judged by the PI or Sub-I to be inappropriate for the study for any reason
Show all 10Show fewer
- For Typically developing participants:
- Known or suspected cognitive impairment
- Known history of MRI abnormality
- Current use of psychotropic medications
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Fondazione Stella Maris
Tirrenia, Tuscany, 56128
Roberta Battini, MD, +39 050886282, roberta.battini@fsm.unipi.it
Laura Baroncelli, PhD, +39 050886233, laura.baroncelli@fsm.unipi.it
About this study
Official title: Establishing Novel Functional Biomarkers for Fragile X Syndrome
The objective of this project is to explore the potential of functional near- infrared spectroscopy (fNIRS) as innovative functional biomarker for clinical trial readiness in Fragile X Syndrome (FXS) that is still without cure. The limited availability of objective and quantitative biomarkers to monitor brain function poses challenges to advancing therapeutic research. With clinical trials on the horizon, the need for precise measurement to evaluate treatment efficacy is pressing. The investigators seek to address this gap by assessing the prognostic reliability of both resting and task- evoked fNIRS. The primary objectives of this pilot study are: 1. to determine the feasibility of fNIRS in individuals with FXS; 2. to collect pilot data on individuals with FXS to determine the patterns of cerebral oxygen consumption as measured by fNIRS; 3. to compare cerebral oxygen consumption changes at rest and from visual/auditory tasks in affected individuals versus age-appropriate healthy volunteers. The secondary objectives of this study are: 1. to correlate cerebral oxygen consumption changes from visual/auditory task in affected individuals to other measures of disease state (e.g., neuropsychological assessment, disease- specific severity rating scales); 2. to examine test-retest reliability of our fNIRS measures in both affected individuals and healthy controls.
Read the detailed description
This is a non-profit study of a cohort of patients with genetically determined Fragile X Syndrome and age-matched healthy controls. The design of the study is observational, case-control. An imaging session using fNIRS (NIRSport2, NIRx Technologies) will be conducted during the visits scheduled for the individual participants. Participants will be assessed for optimal placement of the fNIRS probe on the head through measurement of the fiducial points on the scalp. With the NIRx NIRSPort2 system, the near- infrared sources and detectors are situated in a fabric cap resembling a swim cap that is applied like a hat and secured in place by a velcro chin strap.
Once the probe is placed, fNIRS will be measured during a passive viewing/ listening task administered on a computer. The montage consists of 8 red light-sources operating at 760 nm and 850 nm, and 7 detectors which can be easily placed into a textile EEG cap (EASYCAP, Herrsching, Germany, size according to head circumference). The systems that are utilized have been selected to be very child-friendly systems, involving no cleaning or abrasion of the scalp preparation and rapid application. Application procedures have been designed to minimize any discomfort to the participant. In total, these measurements should take 30-40 minutes to complete (including application of the NIRS cap). Alongside fNIRS, neuropsychological assessments of affected individuals patients will be conducted. The following outcome measures will be collected assessing: i) cognitive performance (Leiter International Performance Scale, 3rd edition, PPVT-5, simple reasoning tasks on tablets and Vineland Adaptive Behaviour Scale); ii) behavioural disorder (BASC-3, ABC-2 scales and BRIEF); iii) autistic-like features (SRS-2 and PPD- MRS). The cognitive tasks were chosen to be adapted to the cognitive deficit of affected individuals. A task on tablets with minimal verbal instruction will allow to assess reasoning abilities in severe to moderate ID patients that could not perform classical Wechsler scale (IQ test). Healthy controls will be asked to return 8-12 weeks post their initial visit to undergo repeat fNIRS testing for the purposes of examining test-retest reliability of the fNIRS measurement. If their schedule allows, affected individuals will also undergo repeat fNIRS testing. fNIRS is safe, non-invasive and generally well tolerated. The information obtained from this study will help identify outcome measures for drug testing in future therapeutic trials.
- Conditions
- Fragile X Syndrome
- Medical subject headings
- Fragile X Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| FXS affected individuals | Individuals with genetic diagnosis of FXS. | |
| Neurotypical controls | Healthy volunteers without known health or medical issues. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting-state functional connectivity
The comparison of resting-state fNIRS signal between affected individuals and healthy controls will allow to detect potential alterations of spontaneous brain activity and functional connectivity
Measured: 3 years
Amplitude of sensory-evoked hemodynamic responses
The analysis of the amplitude of sensory-evoked fNIRS signal will allow to assess whether this parameter is able to discriminate between affected individuals and healthy controls. The signal latency will be analysed as well.
Measured: 3 years
Secondary outcomes (1)
Correlation between neurophysiology endpoints and the response on neuropsychological scale.
The correlation analysis will allow to understand whether alterations of functional connectivity and/or sensory-evoked responses can be predictive of the severity of symptoms
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start1 Jun 2023
- Primary completion15 Jun 2025 (estimated)
- Study completion15 Dec 2025 (estimated)
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 SyndromeStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Fondazione Stella Maris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293027
- Sponsor's protocol ID
- IMAGINER FXS
- Status last verified
- Feb 2024
- First submitted
- 20 Feb 2024
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mazziotti R, Scaffei E, Conti E, Marchi V, Rizzi R, Cioni G, Battini R, Baroncelli L. The amplitude of fNIRS hemodynamic response in the visual cortex unmasks autistic traits in typically developing children. Transl Psychiatry. 2022 Feb 8;12(1):53. doi: 10.1038/s41398-022-01820-5.
PubMed 35136021Scaffei E, Mazziotti R, Conti E, Costanzo V, Calderoni S, Stoccoro A, Carmassi C, Tancredi R, Baroncelli L, Battini R. A Potential Biomarker of Brain Activity in Autism Spectrum Disorders: A Pilot fNIRS Study in Female Preschoolers. Brain Sci. 2023 Jun 14;13(6):951. doi: 10.3390/brainsci13060951.
PubMed 37371429
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establishing Novel Functional Biomarkers for Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT06293027
- Acronym / sponsor ID
- IMAGINER FXS
- Conditions
- Fragile X Syndrome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- IRCCS Fondazione Stella MarisUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 15 Jun 2025 (estimated)
- Study completion
- 15 Dec 2025 (estimated)
- First posted
- 5 Mar 2024 (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.
The objective of this project is to explore the potential of functional near- infrared spectroscopy (fNIRS) as innovative functional biomarker for clinical trial readiness in Fragile X Syndrome (FXS) that is still without cure. The limited availability of objective and quantitative biomarkers to monitor brain function poses challenges to advancing therapeutic research. With clinical trials on the horizon, the need for precise measurement to evaluate treatment efficacy is pressing. The investigators seek to address this gap by assessing the prognostic reliability of both resting and task- evoked fNIRS. The primary objectives of this pilot study are: 1. to determine the feasibility of fNIRS in individuals with FXS; 2. to collect pilot data on individuals with FXS to determine the patterns of cerebral oxygen consumption as measured by fNIRS; 3. to compare cerebral oxygen consumption changes at rest and from visual/auditory tasks in affected individuals versus age-appropriate healthy volunteers. The secondary objectives of this study are: 1. to correlate cerebral oxygen consumption changes from visual/auditory task in affected individuals to other measures of disease state (e.g., neuropsychological assessment, disease- specific severity rating scales); 2. to examine test-retest reliability of our fNIRS measures in both affected individuals and healthy controls.
Detailed description
This is a non-profit study of a cohort of patients with genetically determined Fragile X Syndrome and age-matched healthy controls. The design of the study is observational, case-control. An imaging session using fNIRS (NIRSport2, NIRx Technologies) will be conducted during the visits scheduled for the individual participants. Participants will be assessed for optimal placement of the fNIRS probe on the head through measurement of the fiducial points on the scalp. With the NIRx NIRSPort2 system, the near- infrared sources and detectors are situated in a fabric cap resembling a swim cap that is applied like a hat and secured in place by a velcro chin strap.
Once the probe is placed, fNIRS will be measured during a passive viewing/ listening task administered on a computer. The montage consists of 8 red light-sources operating at 760 nm and 850 nm, and 7 detectors which can be easily placed into a textile EEG cap (EASYCAP, Herrsching, Germany, size according to head circumference). The systems that are utilized have been selected to be very child-friendly systems, involving no cleaning or abrasion of the scalp preparation and rapid application. Application procedures have been designed to minimize any discomfort to the participant. In total, these measurements should take 30-40 minutes to complete (including application of the NIRS cap). Alongside fNIRS, neuropsychological assessments of affected individuals patients will be conducted. The following outcome measures will be collected assessing: i) cognitive performance (Leiter International Performance Scale, 3rd edition, PPVT-5, simple reasoning tasks on tablets and Vineland Adaptive Behaviour Scale); ii) behavioural disorder (BASC-3, ABC-2 scales and BRIEF); iii) autistic-like features (SRS-2 and PPD- MRS). The cognitive tasks were chosen to be adapted to the cognitive deficit of affected individuals. A task on tablets with minimal verbal instruction will allow to assess reasoning abilities in severe to moderate ID patients that could not perform classical Wechsler scale (IQ test). Healthy controls will be asked to return 8-12 weeks post their initial visit to undergo repeat fNIRS testing for the purposes of examining test-retest reliability of the fNIRS measurement. If their schedule allows, affected individuals will also undergo repeat fNIRS testing. fNIRS is safe, non-invasive and generally well tolerated. The information obtained from this study will help identify outcome measures for drug testing in future therapeutic trials.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FXS affected individuals | – | –Individuals with genetic diagnosis of FXS. |
| Neurotypical controls | – | –Healthy volunteers without known health or medical issues. |
Who may qualify
- Ages
- 2 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Fragile X syndrome (FXS) is the most commonly inherited form of mental retardation and developmental disabilities, affecting 1 in 4000 individuals. The phenotype of FXS involves mental retardation or learning disabilities, social deficit, anxiety, attention deficit, impulsivity, hyperarousal, mood instability, inflexibility, prominent ears, long face, and hyperextensible finger joints. There is no effective treatment for FXS, and the standard of care include therapies that help minimise the symptoms of the condition.
Key inclusion criteria (10 listed)
- Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment
- Diagnosed with FXS with a previously identified pathogenic or likely pathogenic variant in the FMR1 gene.
- Must also meet the diagnostic criteria for FXS.
- Male
- Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment
Key exclusion criteria (10 listed)
- Unwilling or unable to comply with study procedures and assessments
- Contraindications to fNIRS, such as uncooperative or destructive behaviors preventing lead placement or capture by fNIRS equipment
- Traumatic loss of consciousness in the last year
- Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
- If participant is judged by the PI or Sub-I to be inappropriate for the study for any reason
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Resting-state functional connectivity
Time frame: 3 years
The comparison of resting-state fNIRS signal between affected individuals and healthy controls will allow to detect potential alterations of spontaneous brain activity and functional connectivity
Amplitude of sensory-evoked hemodynamic responses
Time frame: 3 years
The analysis of the amplitude of sensory-evoked fNIRS signal will allow to assess whether this parameter is able to discriminate between affected individuals and healthy controls. The signal latency will be analysed as well.
1 secondary outcome
Correlation between neurophysiology endpoints and the response on neuropsychological scale.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Background: PubMed 35136021Mazziotti R, Scaffei E, Conti E, Marchi V, Rizzi R, Cioni G, Battini R, Baroncelli L. The amplitude of fNIRS hemodynamic response in the visual cortex unmasks autistic traits in typically developing children. Transl Psychiatry. 2022 Feb 8;12(1):53. doi: 10.1038/s41398-022-01820-5.
- Background: PubMed 37371429Scaffei E, Mazziotti R, Conti E, Costanzo V, Calderoni S, Stoccoro A, Carmassi C, Tancredi R, Baroncelli L, Battini R. A Potential Biomarker of Brain Activity in Autism Spectrum Disorders: A Pilot fNIRS Study in Female Preschoolers. Brain Sci. 2023 Jun 14;13(6):951. doi: 10.3390/brainsci13060951.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fragile X Syndrome, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
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 10 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 5 Mar 2024. 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 Italy. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Roberta Battini, MD (+39 050886282, roberta.battini@fsm.unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting-state functional connectivity (time frame: 3 years). 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 NCT06293027, 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 5 Mar 2024.