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

NCT06279858 | Recruiting DMC

• 1 other identifier: 1-2024
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fragile X Syndrome

Keywords

Fragile X Sindrome; Gut-Brain Axis; Probiotics

Outcome Measures

Primary Outcomes (2)

• 1. Vineland Adaptive Behavior Scales-Third Edition (VABS-III)

  The Vineland, which is a gold standard test for assessing adaptive behavior that is widely used in clinical trials, will be administered to the parent/caregiver at baseline and end of treatment/week 12. Subtests include Communication, Daily Living Skills, Socialization, Motor Skills, and Adaptive Behavior Composite. The Vineland has been normed for individuals with intellectual disability and ASD. The third edition includes updated item content to streamline similar items and reduce redundancy, to reflect changes in daily living (e.g., technology) and in conceptions of developmental disabilities (e.g., ASD), and to allow for potential cultural differences by using more generalized wording of certain items

  3 month

• Eye tracking

  Eye Tracking Measures: Social Gaze and Pupillometry - For individuals with FXS, findings demonstrated that the social gaze measure shows decreased visual fixations on the eye region while viewing human faces (with greater fixation to the nose region), and these individuals show abnormal pupillary dilation, an indication of sympathetic nervous system reactivity, compared with controls \[31\]. During the experiment, individuals with FXS will sit in front of the monitor at the distance of 65 cm, while stimuli consist of human faces in natural size with different emotional expressions will be presented. This eyetracking system has several benefits that make it conducive to testing individuals with developmentaldisorders, including 35 cm x 30 cm of tolerance to head-motion at 65 cm distance without requiring any head apparatus or restraints.

  3 month

Secondary Outcomes (5)

• Clinical Global Impression Scales of Severity (CGI-S) and Improvement (CGI-I) -

  3 month

• The Aberrant Behavior Checklist - Community Edition (ABC-C), scored using the FXS-specific factoring system (ABC-CFX)

  3 month

• Pediatric Quality of Life Questionnaire (PedsQL) Parent Proxy

  3 month

• Child Sleep Habits Questionnaire (CSHQ)

  3 month

• EEG analyses

  3 month

Other Outcomes (1)

• Microbiome analyses

  3 month

Study Arms (1)

Probiotics

EXPERIMENTAL

Each participant receives probiotic for 3 months (12 weeks). Participants act as their own controls by measuring the microbiome and other parameters before and after taking the probiotics. This was chosen because individual's microbiome is highly personalized. The unique composition of an individual's microbiome can have implications for the effectiveness of probiotics. All participants will receive probiotic mixture which contains: (i) Lactobacillus casei BL 2401 (40%), (ii) Lactobacillus salivarius BL 2201 (40%) (iii) Bifidobacterium breve BL 3406 (20%). Total amount is 5 x109 CFU in one HPMC capsule, at the end of the shelf life. These strains are registered and preserved in the French National Collection of Cultures of Microorganisms (CNCM, Collection Nationale de Cultures de Microorganismes). They are on EFSA's QPS (Qualified and Presumption of Safety) list and are considered safe for use in food and dietary products

Dietary Supplement: Probiotics

Interventions

Probiotics DIETARY_SUPPLEMENT

Patients will be recruited and included in the study. At baseline, a detailed medical history, and physical and neurological examination will be carried out, with all medications and medical problems documented for all participants. In the first 4 weeks, each patient will receive a weekly call to evaluate tolerability of the probiotic and any adverse events (AEs). Visit 2 will be organized after 6 weeks and final visit 3 after 12 weeks of study period. Any change in medications will also be documented during visits. The examination and documentation of AEs, will be repeated at each visit, while CGI-I will be scoring at visit 2 and final visit 3. Outcome measures will be repeated at the final followup visit at 3 months/end of treatment. Stool samples will be collected twice, at the baseline and final visits. Analyses of microbiome will be performed once, at the end of the study, when all samples are collected and sent to the selected laboratory.

Probiotics

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Specila hospital for cerebral palsy and developmental neurology: lead
• FRAXA Research Foundation: collaborator

Study Sites (1)

Special Hospital for Cerebral Palsy and Developmental Neurology

Belgrade, 11000, Serbia

RECRUITING

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MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Probiotics

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Dragana Protic, Prof

  University od Belgrade

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dragana Protic, Prof.

CONTACT

+381638493597; dragana.protic@sbcprn.com

Sanja Dimitrijevic, PhD

CONTACT

+381640667466; sanja.dimitrijevic@sbcprn.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is open label trial without masking, where each participant receives probiotic for 3 months (12 weeks). It will be single group assignment. In this approach, participants act as their own controls by measuring the microbiome and other parameters before and after taking the probiotics. This design was chosen because individual's microbiome is highly personalized. Even within a family, individuals can have distinct microbiomes. The unique composition of an individual's microbiome can have implications for the effectiveness of probiotics. Thus, changes in analyses and scores between baseline and 3-month study period will be assessed for everyone. Specifically, microbiome modifications that may be associated with changes in behavior and brain processing will be examined.

Study Record Dates

• First Submitted: February 11, 2024
• First Posted: February 28, 2024
• Study Start: January 1, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)