Probiotic Treatment for Prader-Willi Syndrome

Study Overview
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Brief Summary
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A whole new research area studying the function of intestinal microorganisms, also known as gut microbiota, has emerged during the last decade. As a result, dietary supplementation with specific bacteria (or probiotics) holds great promise as a therapeutic strategy for a wide range of diseases, from obesity to anxiety and depression, all of which are major characteristics of Prader-Willi syndrome (PWS). The main objective of the current proposal is to determine the effects of Bifidobacterium animalis subsp. lactis (strain BPL1) supplementation in children and young adults with PWS. Specifically, participants will receive placebo or BPL1 for 6 months, and then this phase will be followed by a 6-month extension period in which all participants will receive BPL1. This study will allow us to 1) determine the effects on fat mass and glucose metabolism; and 2) explore the effects on mental health symptoms by studying potential structural changes in the brain by magnetic resonance imaging (MRI) as well as using a number of psychiatric questionnaires.

Official Title
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Probiotics as a Long-term Treatment Strategy for Prader-Willi Syndrome

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Probiotic
* Dietary Supplement: Follow-up 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 Patients with bariatric surgery in the last two years Patients with Type 2 Diabetes on insulin therapy Presence of other medical problems that would preclude study participation Unsuitable for inclusion in the study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 30 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>This arm will receive placebo for 6 months then probiotic for 6 more months. | Dietary Supplement: Placebo<br>* Intervention with a daily dose of placebo for 6 months<br>Dietary Supplement: Follow-up probiotic<br>* Intervention with a daily dose of probiotic for 6 months<br>|
| Experimental: Probiotic<br>This arm will receive probiotic for 6 months then will keep receiving probiotic for 6 more months. | Dietary Supplement: Probiotic<br>* Intervention with a daily dose of probiotic for 6 months<br>Dietary Supplement: Follow-up probiotic<br>* Intervention with a daily dose of probiotic for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent body fat content | Body fat content will be measured by dual energy x-ray absorptiometry (DXA) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BMI and BMI z-score | Weight and height will be combined to calculate changes in BMI and BMI z scores from all subjects will be assessed | Baseline, 6, and 12 months | 
| Change in height (cm) | Changes in height from subjects that have not yet reached final height will be measured. | Baseline, 6, and 12 months | 
| Change in insulin sensitivity | Fasting blood glucose and insulin concentrations will be combined to calculate HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). | Baseline, 6, and 12 months | 
| Change in lipid profile (triglyceride, cholesterol) | Blood test after overnight fasting | Baseline, 6, and 12 months | 
| Change in hyperphagia | Measured by the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), specific for subjects with Prader-Willi syndrome (scale 0-36, higher values indicate higher degree of hiperphagia). Parental or caregiver reported. | Baseline, 6, and 12 months | 
| Change in Aberrant Behavior Checklist (ABC) score | The Aberrant Behavior Checklist (ABC) is a 58-item questionnaire. It consists of five subscales: hyperactivity (0-48), lethargy (0-48), stereotypical behavior (0-21), irritability (0-45), and inappropriate speech (0-12). Higher scores indicate worse outcome. Parental or caregiver reported. | Baseline, 6, and 12 months | 
| Change in Repetitive Behavior Scale (RBS) score | The Repetitive Behavior Scale (RBS) measures repetitive behaviors that are related to autism. It consists of 43-items grouped in two different scores: higher-order (ritualistic, sameness, compulsive and restricted subscales; score 0-87) and lower-order (stereotypy and self-injury; score 0-42) repetitive behaviors. Higher scores indicate worse outcome. Parental or caregiver reported. | Baseline, 6, and 12 months | 
| Change in Social Responsiveness Scale (SRS) score | Measured by the validated Social Responsiveness Scale (SRS-2) which assesses autism-related symptoms focusing on social function. Higher values indicate worse outcome. A total score of 76 or higher is considered severe; a score between 66 and 75 is considered moderate; a score between 60 and 65 is considered mild; a score of 59 or lower is considered within normal limits. Parental or caregiver reported. | Baseline, 6, and 12 months | 
| Change in Clinical Global Impression (GCI score) score | Measured by the validated Clinical Global Impression Scale (CGI, scale 0-14, higher values indicate worse outcome). This toll will be completed by the clinician. | Baseline, 6, and 12 months |