Clinical trial NCT03548480: Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment
Official title: Targeting the Gut Microbiome for Prader-Willi Syndrome Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prader-Willi Syndrome
Lead sponsor: Fundació Sant Joan de Déu
Sponsor class: OTHER
First posted: 2018-06-07
Enrollment: 39
Sex: ALL
Minimum age (years): 2
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: 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.


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

Primary outcomes:
measure: Change in percent body fat
timeFrame: 3 months
Secondary outcomes:
measure: Change in lipid profile (triglyceride, cholesterol)
timeFrame: 3 months
measure: Change in glucose metabolic parameters (glucose, insulin, HbA1c)
timeFrame: 3 months
measure: Change in circulating cytokine levels
timeFrame: 3 months
measure: Change in hyperphagia
timeFrame: 3 months
measure: Change in thermoregulation
timeFrame: 3 months
Other outcomes:
measure: Change in plasma metabolome
timeFrame: 3 months
measure: Change in urine metabolome
timeFrame: 3 months
measure: Change in intestinal microbiome
timeFrame: 3 months
Locations:
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
Study officials:
affiliation: Fundació Sant Joan de Déu
name: Carles Lerin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.