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

Obesity, Child Clinical Trial

— OBEGEN  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05938335
• Other study ID #: 2023PI
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: July 2023
• Source: Central Hospital, Nancy, France
• Contact: Emeline RENARD
• Phone: +33383154500
• Email: e.renard[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Obesity, Child
• Obesity, Morbid
• Pediatric Obesity

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical characteristics of children with severe obesity followed in CHRU of Nancy	Description of the clinical characteristics : height in cm BMI	1 year
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics :thyroid function (TSH T3 T4)	1 year
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : IGF1 levels	1 year
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics :BMI in kg/m²	1 year
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : weight in kg	1 year
Secondary	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
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : metabolic profile	1 year
Secondary	Clinical characteristics of children with mutations of leptin melanocortin pathway	Description of the clinical characteristics : leptin level	1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	Clinical characteristics of children with severe obesity followed in CHRU of Nancy	Description of the clinical characteristics :BMI in kg/m²	1 year