Clinical trial NCT06957054: Neural Biomarkers in Fragile X Syndrome
Official title: Assessment of Neural Biomarkers in Adult Subjects With Fragile X Syndrome and Typically Developing Subjects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fragile X Syndrome (FXS)
Neurotypical Adults
Keywords: Fragile X Syndrome
FXS
Fragile X
Neurodevelopmental Disorders
Central Nervous System Diseases
Intellectual Disability
Neurobehavioral Manifestations
Genetic Diseases, X-Linked
Congenital Abnormalities
Orphan Diseases
Rare Diseases
Neural biomarkers
Lead sponsor: Connecta Therapeutics, S.L.
Sponsor class: INDUSTRY
Collaborators: name: Hospital del Mar Research Institute (IMIM)
name: Corporacion Parc Tauli
name: Ministry of Science and Innovation, Spain
First posted: 2025-05-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Fragile X syndrome adult patients compared to neurotypical adults

Brief summary: The purpose of this non-interventional test /re-test study is to assess neural biomarkers in adult subjects with Fragile X syndrome compared to those measured in a population of typically developing adults

Detailed description: This study consists of a screening period and two cross sectional evaluations assessed in one month interval (test/re-test), first on the Visit 1 (Basal) and the other on the Visit 2 (end-of-study visit, EOS).

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.

Primary outcomes:
measure: Cognitive profile of FXS patients compared to neurotypical subjects using the NIH-TCB-ID Toolbox
timeFrame: Day 1 and Day 28 (± 3 days)
measure: Neural oscillations using Electroencephalography (EEG)
timeFrame: Day 1
measure: Point of gaze using eye tracking
timeFrame: Day 1 and Day 28 (± 3 days)
measure: Behavior troubles of the FXS patients compared to neurotypical subjects using the Aberrant Behavior Checklist (ABC)
timeFrame: ≤ 1 month prior to Day 1
measure: Adaptative functioning using the Vineland Adaptive Behaviour Scale (VABS-3)
timeFrame: ≤ 1 month prior to Day 1
measure: Clinician-rated global functioning using the Clinical Global Impression (CGI)
timeFrame: ≤ 1 month prior to Day 1 and Day 28 (± 3 days)
measure: Stress biomarkers of the FXS patients compared to neurotypical subjects measured by cortisol concentrations in hair (occipital area)
timeFrame: ≤ 1 month prior to Day 1
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects determining vitamin D (25-Hydroxy) concentrations in serum
timeFrame: Day 1 and Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects determining 24h urine cortisol concentrations
timeFrame: Day 1 and Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using sleep diaries
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: number of days
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of wear
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: total steps
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: steps per day
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: average of energy expenditure
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of sedentary physical activity
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of light physical activity
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of moderate physical activity
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of vigorous physical activity
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: percentage of very vigorous physical activity
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: bedtime
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: wake-up time
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: mean time in bed
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: total mean sleep time
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: sleep efficiency
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: wake after sleep onset
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: average of awakening
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Biorhythm characteristics of FXS patients compared to neurotypical subjects using actigraphy: hours spent awake at night
timeFrame: From Day 1 to Day 28 (± 3 days)
measure: Quality of life of the FXS patients compared to neurotypical subjects using the Paediatric Quality of Life Inventory (PedsQL)
timeFrame: ≤ 1 month prior to Day 1
measure: Quality of sleep of the FXS patients compared to neurotypical subjects using Pittsburgh sleep quality index (PSQI)
timeFrame: Day 1 and Day 28 (± 3 days)
measure: FMRP protein in peripheral blood of FXS patients in peripheral blood compared to neurotypical subjects
timeFrame: ≤ 1 month prior to Day 1
measure: miRNA profile of FXS patients in plasma compared to neurotypical subjects
timeFrame: Day 1 and Day 28 (± 3 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Sabadell
country: Spain
facility: Consorci Corporació Sanitaria Parc Taulí. Institut Investigació i Innovació Parc Taulí (I3PT)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar Research Institute (HMRI)
Study officials:
affiliation: Hospital del Mar Research Institute
name: Rafael De la Torre Fornell, Pharm, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Consorci Corporació Sanitària Parc Taulí. Institut d'Investigació i Innovació Parc Taulí (I3PT)
name: Ana Roche Martínez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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