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

• ClinicalTrials.gov Identifier: NCT03548480
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Last Update Posted: March 5, 2020
• Sponsor: Fundació Sant Joan de Déu
• Information provided by (Responsible Party): Fundació Sant Joan de Déu

Tracking Information

• First Submitted Date: May 2, 2018
• First Posted Date: June 7, 2018
• Last Update Posted Date: March 5, 2020
• Actual Study Start Date: January 1, 2018
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 6, 2018)

Change in percent body fat [ Time Frame: 3 months ]

Measured by DXA scan

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 6, 2018)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 6, 2018)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment
• Official Title: Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prader-Willi Syndrome

Intervention

• Dietary Supplement: Placebo
  Intervention with a daily dose of placebo
• Dietary Supplement: Probiotic
  Intervention with a daily dose of probiotic

Study Arms

• Placebo Comparator: Placebo
  Intervention: Dietary Supplement: Placebo
• Experimental: Probiotic
  Intervention: Dietary Supplement: Probiotic

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2020): 39
• Original Estimated Enrollment (submitted: June 6, 2018): 40
• Actual Study Completion Date: January 31, 2019
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 19 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT03548480
• Other Study ID Numbers: FSJD-BALPWS-2018
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fundació Sant Joan de Déu
• Original Responsible Party: Same as current
• Current Study Sponsor: Fundació Sant Joan de Déu
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Carles Lerin, PhD; Fundació Sant Joan de Déu

• PRS Account: Fundació Sant Joan de Déu
• Verification Date: March 2020