Probiotic Treatment for Prader-Willi Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Follow-up probiotic; Dietary supplement: Probiotic

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in intestinal microbiota composition	DNA isolated from fecal samples will be analyzed by sequencing the hypervariable region of the bacterial 16S gene.	Baseline, 6, and 12 months
Change in plasma metabolome	Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of plasma samples	Baseline, 6, and 12 months
Changes in brain structural anatomy	Subjects older that 12 years of age will undergo brain magnetic resonance imaging (MRI). Changes in orbitofrontal cortex, amygdala, hypothalamus, and total gray matter volume will be evaluated.	Baseline, 6, and 12 months

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu
• Investigators: Principal Investigator: Marta Ramon-Krauel, Hospital Sant Joan de Deu

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: PIC-194-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No