Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment

Study Overview
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Brief Summary
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The gut microbiome has recently emerged as a major contributor to obesity, systemic inflammation, and metabolic disease. Furthermore, intestinal bacteria are crucial players in the gut-brain axis, regulating a broad range of central nervous system processes, from satiety mechanisms to anxiety and social behavior. Thus, targeting the microbiome is being actively investigated as a therapeutic strategy for a wide array of diseases, including obesity, anxiety, depression, and autism. Among all intestinal bacteria, Bifidobacterium animalis spp. lactis (BAL) has shown promise for obesity treatment in experimental animal models and human subjects, improving body composition and metabolic health, and reducing energy intake. Moreover, tryptophan metabolism, a crucial regulator of satiety mechanisms and anxiety, is a main target of BAL. Given that clinical manifestations of Prader-Willi syndrome (PWS) include hyperphagia, anxiety, altered body composition, and metabolic dysregulation, the aforementioned effects of BAL might prove highly beneficial for children with PWS. Here, the investigators will test this hypothesis by performing a randomized double-blinded placebo-controlled crossover clinical study to assess the effects of BAL supplementation on an array of clinical manifestations of PWS. Children with PWS will undergo a 3-month placebo/probiotic treatment period, a 3-month washout period, followed by a 3-month probiotic/placebo supplementation. Anthropometric, biochemical, and psychological data as well as biological samples will be obtained at the beginning of the study, and after each of the study periods, with a total of four time-points. Specifically, the investigators will determine body composition by DXA analysis; metabolic health by assessing glucose and lipid metabolic parameters as well as circulating hormonal and cytokine levels; thermoregulation by non-invasive thermal imaging; and hyperphagia and emotional and behavioral problems by applying parental-rated validated questionnaires.

Official Title
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Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Probiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with Prader-Willi Syndrome with genetic confirmation On a stable diet and medication regimen for at least the last two months before enrollment Exclusion Criteria: Current enrollment in or discontinuation within the last 30 days from a clinical trial Presence of other medical problems that would preclude study participation Patients with a history of bariatric surgery Unsuitable for inclusion in the study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Intervention with a daily dose of placebo<br>|
| Experimental: Probiotic<br> | Dietary Supplement: Probiotic<br>* Intervention with a daily dose of probiotic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent body fat | Measured by DXA scan | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipid profile (triglyceride, cholesterol) | Blood test after overnight fasting | 3 months | 
| Change in glucose metabolic parameters (glucose, insulin, HbA1c) | Blood test after overnight fasting | 3 months | 
| Change in circulating cytokine levels | Quantified in plasma samples | 3 months | 
| Change in hyperphagia | Measured by validated questionnaire (HQ-CT) | 3 months | 
| Change in thermoregulation | Measured by thermal imaging | 3 months |