Clinical trial NCT02529085: PWS European Blood Bank for Infants and Controls From 0 to 48 Months
Official title: Study of Early Endocrine Profile in Infants With Prader-Willi Syndrome (PWS) in Order to Unravel the Switch From Early Feeding Difficulties to Obesity and Hyperphagia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prader-Willi Syndrome
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: European Society for Paediatric Endocrinology
First posted: 2015-08-19
Enrollment: 215
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The present project aims to determine the underlying mechanisms for the switch from failure to thrive to excessive weight gain and hyperphagia with impaired satiety in PWS. The primary objective is to describe the evolution of circulating hormones involved in feeding and appetite regulation during the 4 first years of life. The secondary objective is to make this blood bank available for other research projects and particularly the investigation of hormones involved in hypogonadism.

Over the last ten years, the age at diagnosis in PWS has fallen significantly and the majority of cases is now diagnosed during the 1st trimester of life giving the possibility to collect precise clinical data and serum samples at early stages. The investigators of the project are involved in the care of patients with PWS and have a devoted clinic and an organized network in their country through clinical networks or patient associations.

Detailed description: The investigators propose to perform a prospective multicentric study, both longitudinal (duration 30 months) and cross-sectional with implementation of a blood bank in link with a multicenter database including clinical data on birth, auxology, endocrine functions and feeding behaviour. The cohort will include 200 infants from 3 to 48 months with PWS and 200 controls matched on age recruited in the 6 participating countries. The investigators make the assumption that 3 blood sampling will be necessary during the first year and 6 monthly sampling thereafter. For measuring hormones and neuropeptides (ghrelin, insulin, leptin, pancreatic polypeptide, oxytocin, cortisol, melatonin, orexin A, GLP-1 and PYY) involved in feeding and appetite regulation the investigators will use primarily multiplex microplates technics requiring 50-200µl of sample. Intragroup and intergroup comparisons will be performed in order to describe the evolution of each hormone with time and to compare data obtained in the PWS group with those obtained in the control group.

Eligibility criteria: Inclusion Criteria (PWS infants cohort)

* Genetic diagnosis of Prader-Willi syndrome

Exclusion Criteria (PWS infants cohort)

* none

Inclusion Criteria (control group)

* children hospitalized for a planned surgery for malformation, orthopaedic or visceral surgery

Exclusion Criteria (control group)

* children with endocrine disorder

Primary outcomes:
measure: Levels of hormones and neuropeptides
timeFrame: 42 months
Secondary outcomes:
measure: Correlation between hormones and neuropeptides levels
timeFrame: 42 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Unité d'Endocrinologie Pédiatrique / Université Catholique de Louvain
city: Toulouse
country: France
facility: Department of Pediatrics / Division of Endocrinology
state: Haute-Garonne
city: Essen
country: Germany
facility: Department of Endocrinology / University Children's Hospital
city: Rotterdam
country: Netherlands
facility: Department of Pediatrics / Division of Endocrinology / Erasmus University Medical Center / Sophia Children's Hospital Rotterdam
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: London
country: United Kingdom
facility: Metabolic & Molecular Imaging Group / MRC Clinical Sciences Centre / Imperial College London / Hammersmith Hospital
Study officials:
affiliation: University Hospital, Toulouse
name: Maithe TAUBER, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cadoudal T, Buleon M, Sengenes C, Diene G, Desneulin F, Molinas C, Eddiry S, Conte-Auriol F, Daviaud D, Martin PG, Bouloumie A, Salles JP, Tauber M, Valet P. Impairment of adipose tissue in Prader-Willi syndrome rescued by growth hormone treatment. Int J Obes (Lond). 2014 Sep;38(9):1234-40. doi: 10.1038/ijo.2014.3. Epub 2014 Jan 10.
citation: Beauloye V, Diene G, Kuppens R, Zech F, Winandy C, Molinas C, Faye S, Kieffer I, Beckers D, Nergardh R, Hauffa B, Derycke C, Delhanty P, Hokken-Koelega A, Tauber M. High unacylated ghrelin levels support the concept of anorexia in infants with prader-willi syndrome. Orphanet J Rare Dis. 2016 May 4;11(1):56. doi: 10.1186/s13023-016-0440-0.