Sequencing of 14 Genes From Leptin Melanocortin Pathway in Severe Obesity in Childhood. (OBEGEN)

Results of Sequencing of a Large Panel of Genes From Leptin Melanocortin Pathway in Children Suffering From Severe Obesity

About 380 million children and adolescents suffer from overweight and obesity at the global level. Obesity results from the interplay between biological (sex, age, fetal programming, gut microbiota, epigenetics, and genetics) and environmental factors (e.g., unhealthy diet, physical inactivity, stress). Mutations in genes from leptin melanocortin pathway are involved in "non syndromic monogenic obesity", characterized by severe early onset obesity, hyperphagia and endocrine deficiencies. Exact frequencies of mutation in these genes are not precisely evaluated in french children with severe obesity. Moreover new treatment, such seltmelanotide are avalaible in case of certain mutation, leading to a significative weight loss in treated patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity, Child
• Intervention / Treatment: Genetic: sequencing of a panel of 14 genes in leptin melanocortin pathway

Detailed Description

Obesity is a global health concern that affected more than 650 million adult people and more than 380 million children and adolescents worldwide, with no signs of slowing down despite major investments in health policy. Obestiy is a multifactorial disease, but 40 to 75% of body mass index (BMI) variation is explained by genetic factors.

Mutations in genes from leptin melanocortin pathway lead to "non syndromic monogenic obesity", characterized by severe early onset obesity, hyperphagia and endocrine deficiencies. This pathway plays a central role in regulating mammalian food intake, energy expenditure and body weight regulation. Somes genes are well characterized such LEP gene, LEPR gene, or MC4R but others have been recently described as ADCY3, SIM1, SH2B1, NTRK2, BDNF, KSR2.

The frequency of these mutations are not precisely estimated in a group of french children with severe obesity.

Moreover, a precocious identification of these mutations, could afford, in certain case the possibility of a efficient treatment with setmelanotide, leading to a significant weight loss in treated patients.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emeline RENARD; Phone Number: +33383154500; Email: e.renard@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• severe obesity with BMI > 3SDS

Exclusion Criteria:

• genetic obesity (Prader Willi syndrome, Bardet Biedl syndrome, X fragile syndrome, Alstrom syndrome)
• BMI < 3 SDS
• age < 6 months
• monogenic non syndromic obesity, with mutation in genes of leptin melanocortin pathway previously diagnosed
• cushing syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: severe obese children; children with severe obesity with BMI > 3sds	Genetic: sequencing of a panel of 14 genes in leptin melanocortin pathway; sequencing (NGS) of a panel of 14 genes in leptin melanocortin pathway in french children with severe obesity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of mutations of genes from leptin melanocortin pathway	Evaluating of the frequency of mutations of 14 genes from leptin melanocortin pathway (LEP, LEPR, POMC, PCSK1, MC3R, MC4R, MRAP2, ADCY3, SIM1, SH2B1, NTRK2, BDNF, KSR2) in a group of french children with severe obesity.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical characteristics of children with severe obesity followed in CHRU of Nancy	Description of the clinical characteristics : height in cm BMI	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics :thyroid function (TSH T3 T4)	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : IGF1 levels	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics :BMI in kg/m²	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : weight in kg	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : bone age (X ray of the left hand)	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : metabolic profile	1 year
Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : leptin level	1 year
Penetrance of mutations from leptin melanocortin pathway	Evaluation of the penetrance of mutation from leptin melanocortin pathway, that is to say the percentage of obesity in mutation carrier	1 year
effect of age, sex, country of birth on mutations' penetrance.	Evaluation of the effect of age, sex, country of birth on mutations' penetrance.	1 year
Clinical characteristics of children with severe obesity followed in CHRU of Nancy	Description of Clinical characteristics of children with severe obesity followed in CHRU of Nancy : weight in kg Description of the clinical characteristics :	1 year
Clinical characteristics of children with severe obesity followed in CHRU of Nancy	Description of the clinical characteristics :BMI in kg/m²	1 year

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity; Obesity, Morbid
• Other Study ID Numbers: 2023PI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No