Neural Biomarkers in Fragile X Syndrome | NCT06957054

NCT06957054

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Hospital del Mar Research Institute (IMIM)	OTHER
Corporacion Parc Tauli	OTHER
Ministry of Science and Innovation, Spain	OTHER_GOV

Label	Type	Description	Intervention Names
Group 1		Fragile X syndrome	Other: Any
Group 2		Typically Developing Subjects	Other: Any

Name	Type	Description	Arm Group Labels	Other Names
Any	Other	Any	Group 1 Group 2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cognitive profile of FXS patients compared to neurotypical subjects using the NIH-TCB-ID Toolbox	The NIH-Toolbox Cognitive Battery for Intellectual Disabilities (NIH-TCB-ID) provides a reliable, validated and standardized measure (composite scores) that can be used as efficacy endpoints in clinical studies in patients with neurodevelopmental disorders from 3 to 85 years old. The Fluid Cognition composite score of the NIH Toolbox cognitive battery combines the scores of five tests assessing the following cognitive domains: i) Cognitive flexibility, ii) Inhibitory control and visual attention, iii) Episodic memory, iv) Processing speed and v) Working memory.	Day 1 and Day 28 (± 3 days)
Neural oscillations using Electroencephalography (EEG)	Multichannel EEG will be recorded using a mobile wireless helmet for high precision EEG monitoring. In total, 20 EEG channels will be used to capture brainwave activity. The EEG test contains three well differentiated sections: auditory oddball, resting-state (eyes open and eyes closed) and auditory steady-state response (ASSR). Before starting the auditory oddball, the subject will conduct a training section (40 seconds) to present the type of sounds and to check that they have understood the task by practicing it.	Day 1
Point of gaze using eye tracking	Eye tracking technology will be used to record X and Y coordinates of eye position and pupil diameter. Stimuli will consist on 60 coloured photographs of adult human faces (equal numbers of males and females; different races and ethnicities), each face exhibiting a calm, happy, or fearful expression, and 60 scrambled versions of the face images. Testing will be conducted in a quiet room with the lights turned off. Each trial will start with presentation of a scrambled face image for 1 s followed immediately by its matched face image for 3 s. An inter-trial interval (ITI) containing a uniform grey screen will be shown for 0.5, 1, or 2 s, randomly determined. The order of face presentation will be pseudorandomized and each eye tracking session will last approximately 6 min.	Day 1 and Day 28 (± 3 days)

Eligibility Module

Eligibility Criteria

Demographics common to all subjects:

Male or female subjects.
Age ≥ 18 and ≤ 55 years.
Weight ≥ 50 kg and ≤ 100 kg.
Body mass index (BMI) ≥ 18.5 and ≤ 30.

Subjects with Fragile X syndrome Inclusion Criteria:

Clinical and molecular diagnosis of Fragile X syndrome (> 200 CGG repeats in the promoter region of the FMR1 gene).
Legal representative understands and accepts the study procedures. If only one parent signs, he/she should confirm that the other parent does not object to the patient's participation in the research project.
Subject assenting and/or willing to participate.
Signed informed consent by a legal representative before any study-mandated procedure.
Subject is independently mobile and has sufficient vision and hearing to participate in study evaluations. They must be able to be understood most of the time and must not use other forms of communication, signs, symbol boards or devices as their primary form of communication.
Subjects must have a parent, or other reliable caregiver, who agrees to accompany the subject to all study visits, provide information about the subject as required by the protocol, and ensure compliance with study tests.
Subjects are expected to complete all procedures scheduled during the study visits.

Subjects with Fragile X syndrome Exclusion Criteria:

Personal history of infantile spasms/convulsions/epilepsy, severe head trauma or CNS infections (e.g. meningitis), with the exception of infantile febrile seizures.
Subjects with a current diagnosis including severe autism spectrum disorder or any primary psychiatric diagnosis according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-DSM-5). Diagnoses that are secondary, such as attention deficit hyperactivity disorder, depressive disorders and conduct disorders are allowed as long as they are considered to not interfere with study conduct and are stable during the 3 months before inclusion. Related allowed treatments must be on stable dosing for the last 3 months.
Substance use disorder according to the DSM-5 criteria.
Epileptiform abnormalities (excluding isolated sharp waves and beyond those expected for age).
Any life-threatening disease.
Any other clinically relevant concomitant disease or condition or finding at screening that in the judgment of the investigator could interfere with, the treatment thereof might interfere with, the conduct of the study and related procedures and/or might bias the study results interpretation, or could jeopardize the subject's safety.
Any clinically significant findings in physical examination including vital signs.
Neuroleptic or antidepressant (ISRS) drugs within 3 months before inclusion, except for sertraline at a maximum 100 mg/day, and stable for the last 3 months before inclusion.
Any prescription or over-the-counter drug (except occasional use of paracetamol) in the last 2 weeks before screening.
Patient included in a clinical study with drugs in the last three months prior to inclusion.

Typically Developing Subjects Inclusion Criteria:

Abstinence for any drug abuse 72 hours prior to the screening visit and the observation days, except for nicotine (24 hours).
Able to read Spanish and/or Catalan and to adhere to the study requirements.
Signed informed consent prior to any study-mandated procedure.

Typically Developing Subjects Exclusion Criteria:

Life-time clinically significant cardiovascular, renal, pulmonary, hepatic, onco-haematological, endocrine, gastrointestinal, mental or neurological disease.
Any other clinically relevant concomitant disease or condition or finding at screening that in the judgment of the investigator could interfere with, the treatment thereof might interfere with, the conduct of the study and related procedures and/or might bias the study results interpretation, or could jeopardize the subject's safety.
Any clinically significant findings in physical examination including vital signs.
Neuroleptic drugs within 3 months prior to inclusion.
Any prescription or over-the-counter drug (except occasional use of paracetamol) in the last 2 weeks before screening.
Patient included in a clinical study with drugs in the last three months before inclusion.
Personal history of infantile spasms/convulsions/epilepsy, severe head trauma or CNS infections (e.g. meningitis), except for infantile febrile seizures.
Subjects with a current diagnosis including autism spectrum disorder or any primary psychiatric diagnosis according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-DSM-5). Diagnoses that are secondary, such as attention deficit hyperactivity disorder, depressive disorders and conduct disorders are allowed as long as they are considered to not interfere with study conduct and are stable during the 3 months before inclusion. Related allowed treatments must be on stable dosing for the last 3 months.
Substance use disorder according to the DSM-5 criteria except for mild alcohol use disorder and/or mild or moderate nicotine use disorder.
Positive urine test for drugs of abuse or alcohol breath test at screening.
Epileptiform abnormalities (excluding isolated sharp waves and beyond those expected for age).
Any life-threatening disease.

Name	Affiliation	Role
Rafael De la Torre Fornell, Pharm, PhD	Hospital del Mar Research Institute	Principal Investigator
Ana Roche Martínez, MD, PhD	Consorci Corporació Sanitària Parc Taulí. Institut d'Investigació i Innovació Parc Taulí (I3PT)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hospital del Mar Research Institute (HMRI)		Barcelona	Barcelona	08003	Spain
Consorci Corporació Sanitaria Parc Taulí. Institut Investigació i Innovació Parc Taulí (I3PT)

PubMed Identifier	Type	Citation	Retractions
35322102	Background	Sotoudeh Anvari M, Vasei H, Najmabadi H, Badv RS, Golipour A, Mohammadi-Yeganeh S, Salehi S, Mohamadi M, Goodarzynejad H, Mowla SJ. Identification of microRNAs associated with human fragile X syndrome using next-generation sequencing. Sci Rep. 2022 Mar 23;12(1):5011. doi: 10.1038/s41598-022-08916-4.
36313066	Background

ID	Term
D005600	Fragile X Syndrome
D065886	Neurodevelopmental Disorders
D002493	Central Nervous System Diseases
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D040181	Genetic Diseases, X-Linked
D000013	Congenital Abnormalities
D035583	Rare Diseases

ID	Term
D038901	X-Linked Intellectual Disability
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D025064	Sex Chromosome Disorders