Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment (BALPWS)

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 39
• 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: 2 years to 19 years (ADULT, CHILD)
• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Dietary supplement: Placebo; Intervention with a daily dose of placebo
EXPERIMENTAL: Probiotic	Dietary supplement: Probiotic; Intervention with a daily dose of probiotic

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma metabolome	Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of plasma samples	3 months
Change in urine metabolome	Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of urine samples	3 months
Change in intestinal microbiome	DNA isolated from fecal samples will be analyzed by sequencing.	3 months

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu

Publications and helpful links

General Publications

• Amat-Bou M, Garcia-Ribera S, Climent E, Piquer-Garcia I, Corripio R, Sanchez-Infantes D, Villalta L, Elias M, Jimenez-Chillaron JC, Chenoll E, Ramon D, Ibanez L, Ramon-Krauel M, Lerin C. Effects of Bifidobacterium animalis Subsp. lactis (BPL1) Supplementation in Children and Adolescents with Prader-Willi Syndrome: A Randomized Crossover Trial. Nutrients. 2020 Oct 13;12(10):3123. doi: 10.3390/nu12103123.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): January 31, 2019
• Study Completion (ACTUAL): January 31, 2019

Study Registration Dates

• First Submitted: May 2, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (ACTUAL): June 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

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: FSJD-BALPWS-2018

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
• product manufactured in and exported from the U.S.: No