Probiotic Intervention for Microbiome Modifications and Clinical Improvements in Fragile X Syndrome
Status: Recruiting

The primary objective of this clinical trial is to evaluate efficacy of probiotic mixture which contains Lactobacillus casei, Lactobacillus salivarius and Bifidobacterium breve, in children with Fragile X aged 3-18 years. Specifically, links between microbiome modifications by probiotic mixture and behavioral manifestations and brain processing (eye tracker, EEG analysis) will be assessed. Exploratory objects of this trial are analyses of microbiome composition and assessment of its alterations and modifications (by probiotic mixture) that may lead to clinical improvement and prediction which patients with FXS may be likely to benefit from probiotics treatment.

This is open label trial without masking, where each participant receives probiotic for 3 months (12 weeks). It will be single group assignment. The study plans to enroll 15 participants with FXS, aged 3-18 years, both sexes, during 1-year period and complete all study-related activities by January 2025. During the 3-month study period, subjects will attend three visits (screening/baseline, 6-week, and 3-month visits) to the Fragile X Clinic at the Special Hospital for Cerebral Palsy and Developmental Neurology, Belgrade, Serbia. The primary outcome measureswill be Vineland Adaptive Behavior Scales-Third Edition (VABS-III) and eye tracking measures (social gaze and pupillometry). Exploratory endpoint will be microbiome analyses. Secondary outcome measures will be: CGI-S and CGI-I scores, ABC-CFX score, quality of life, sleep habits and EEG analyses.

Eligibility:
- EligibilityCriteria: Inclusion Criteria:  Subject has Fragile X syndrome with a molecular genetic confirmation of the full FMR1 mutation or mosaicism. Subject is a male or female age 3 to 18 years. Subject must have a parent or caretaker who is willing to participate in the whole study. Subject and caregiver are able to attend the clinic regularly and reliably. Subject and/or subject's parent/legal authorized representative is able to understand, read, write and speak Serbian fluently to complete study-related materials. Behavioral and other non-pharmacological treatments/interventions must be stable for 4 weeks before screening and must remain stable during the period between screening and the commencement of study probiotic, and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a school program, due to school vacations, are allowed. The use of concomitant medications must be stable, in terms of dose and dosing regimen, for at least 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of the study; every effort should be made to maintain stable regimens of allowed concomitant medications from the time of commencement of double-blind study medication until the last study assessment. Patient's parent(s), legal authorized guardian(s), or consistent caregiver(s) can understand and sign an informed consent form to participate in the study. For subjects who are not their own legal guardian, subject's parent/legal authorized representative is able to understand and sign an informed consent to participate in the study. Subject and/or subject's parent/legal authorized representative is able to understand, read, write, and speak Serbian fluently to complete study-related materials.  Exclusion Criteria:  Families that are not cooperative and will not follow through with the demands of this study; Antibiotic use in the last two months (not counting topical antibiotics); Currently taking antibiotics; Any changes in medications, nutritional supplements, therapies, in the last two months, or any plans to change them during the first 3 months of probiotic treatment; Diagnosis of severe gastrointestinal diseases, such as Crohn's Disease, or Ulcerative Colitis; Subject has a life-threatening medical problem or other major systemic illness that compromises health or safety and/or would interfere with this study; Age younger than 3 or older than 18 years. - HealthyVolunteers: No - Gender: All - MinimumAge: 3 Years - MaximumAge: 18 Years - StdAgeList: Child, Adult