Clinical trial NCT04632511: Metabotyping of Overweight and Obese Children
Official title: Metabotyping of Overweight and Obese Children Towards Early Detection of Insulin Resistance and Low-grade Inflammation by Means of a Rectal Sampler
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Metabolic Disease
Obesity, Infant
Keywords: metabolomics
mass spectrometry
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
name: Universitair Ziekenhuis Brussel
name: Algemeen Ziekenhuis Maria Middelares
name: AZ Jan Palfijn Gent
name: AZ Sint-Lucas Gent
name: University Hospital, Antwerp
name: AZ Alma
name: AZ Sint-Jan AV
First posted: 2020-11-17
Enrollment: 232
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Children with overweight and obesity and normal-weight children
Primary purpose: SCREENING

Brief summary: Today's children are increasingly facing metabolic-related health issues, among which the worldwide prevalence of overweight and obesity is rising at an alarming pace. Childhood obesity is associated with the early onset of chronic diseases including an emergence of prediabetes and diabetes mellitus type 2. The decline of insulin sensitivity already years before puberty, exposes children to long- term complications prior the appearance of clinical symptoms and time of diagnosis. The shortened life expectancy and large economic burden imposed underlines the need for the identification of metabotypes at risk at an early stage. One's genetics, microbial gut composition and every aspect of the environment in which children are raised have been implicated in diet-related obesity rendering metabolomics a very powerful tool towards precision medicine. Yet, the excellence of stool in reflecting the intertwining thereof is completely unexplored for pediatric purposes, whereas blood sampling causing pain and stress for child and parent only captures a narrow fraction of the metabolome. As such, rectal sampling using a customised medical swab for optimal gut metabolome coverage is envisioned. Ambient laser desorption ionisation will be hyphenated to high-resolution mass spectrometry-based metabolomics to provide a framework for elucidating predictive and/or prognostic biomarkers for ever-increasing pediatric metabolic diseases such as obesity and (pre)diabetes.

Detailed description: The impetus for this research proposal stems from the ever-increasing metabolic-related health issues impacting today's children. Particularly, the high prevalence of childhood obesity accompanied by substantial progression to 'prediabetic state' at teen age and full-blown DMT2, the most prevailing endocrine disease worldwide, at early adulthood. Several risk factors for the development of overt DMT2 and crescent atherogenic processes, including unhealthy lifestyle patterns, decreased physical activity and (subsequent) obesity, that may be considered markers of metabolic abnormalities, such as insulin resistance, are already well-established in children with impaired glucose tolerance prior to time of diagnosis around early adolescence. Moreover, even in individuals with normal glucose tolerance, insulin resistance has been pointed out a major risk factor and predictor for the development of DMT2. Conversely, the micro- and macrovascular events do not readily appear until maturity, thereby predisposing obese children to the development of several long-term complications urging the quest for diagnostic, prognostic and/or predictive biomarkers for insulin resistance and related metabolic diseases. Hence, intervening in the pre-pubertal life stage becomes of paramount importance. As a pivotal component in precision medicine, and unlike routine measurements that only include a narrow set of blood chemistry analytes, metabolomics reveals a far more comprehensive metabolic signature. Taken together that DM and related comorbidities are considered metabolic diseases with a dysregulated lipid metabolism being a central factor in the pathogenesis, metabolomics (and in particular lipidomics) is of key importance in this research proposal. Furthermore, given the collision between genes, gut microbiota and environmental changes preceding the development of DM and, in addition, the excellence of stool in reflecting the metabolic interactions and outcomes thereof, an innovative rectal sampler using a medical swab with customized surface tip for optimal gut metabolome coverage will be used. REIMS significantly reduces time (\< 10 s) and workload (minimal sample preparation), enhancing research output and efficiency. The aim is the early identification of children who are destined to develop obesity-related chronic diseases.

Eligibility criteria: Inclusion Criteria:

* prepubertal

Exclusion Criteria:

* no diabetes type 1 or 2, no endocrine disease, no chronic medication

COHORT NAME: MetaBEAse

Primary outcomes:
measure: rectal MetaSAMP
timeFrame: 2 years
Secondary outcomes:
measure: Metabolome markers
timeFrame: 4 years
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University
state: East-flanders
city: Eeklo
country: Belgium
facility: AZ Alma
state: Oost-Vlaanderen
city: Zottegem
country: Belgium
facility: AZ Sint-Elisabeth
state: Oost-Vlaanderen
city: Waregem
country: Belgium
facility: OLV Lourdes Waregem
state: West-Vlaanderen
city: Antwerp
country: Belgium
facility: UZA
city: Bruges
country: Belgium
facility: AZ Sint-Jan Brugge
city: Ghent
country: Belgium
facility: General Hospital Jan-Palfijn
city: Ghent
country: Belgium
facility: General Hospital Sint-Lucas
city: Jette
country: Belgium
facility: University Hospital Brussels
city: Leuven
country: Belgium
facility: University Hospital Leuven
Study officials:
affiliation: University Ghent
name: Jean De Schepper
role: PRINCIPAL_INVESTIGATOR
References: