Study of the Molecular Basis in the Pathophysiology of Food Intake and Growth in Children (Ghrelin)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by HaEmek Medical Center, Israel.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
NCT00830141
First received: January 25, 2009
Last updated: January 26, 2009
Last verified: January 2009
  Purpose

Obesity, now a global epidemic, is a leading cause of illness and mortality in the developed world. To better understand the pathophysiological mechanisms that underlie weight disorders, increasing attention is being paid to central regulatory elements in energy homeostasis, including food intake and energy expenditure. The human hormone ghrelin is secreted as a preprohormone (preproghrelin), from which two hormones with antagonistic effects are derived: ghrelin, which has orexigenic effects and obestatin, which has anorexigenic effects. Ghrelin's actions are mediated by GH secretagogue receptor (GHSR). Ghrelin synthesis occurs predominantly in epithelial cells of the fundus of the stomach. . As the ligand for GHSR, ghrelin stimulates secretion of GH. In both rodents and humans, ghrelin regulates hunger though its action on hypothalamic feeding centers. Other effects of ghrelin include stimulating gastric emptying, positive effects on cardiovascular function, increasing intestinal peristalsis, and positive exocrine and paracrine pancreatic secretion. Despite its important physiological role, its precise regulatory mechanisms remain ambiguous. Thus, it has been suggested that mutations in ghrelin and its receptor will present clinically with obesity, eating disorders or growth disturbances. To date, only four different mutations have been reported in GHSR and no mutations have been found in the ghrelin gene.

Working hypothesis and aims: We hypothesize that mutations in ghrelin or in its receptor, GHSR, affect appetite regulation and cause growth and eating disorders.


Condition
Obesity
Short Stature

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Study of the Molecular Basis in the Pathophysiology of Food Intake and Growth in Children

Resource links provided by NLM:


Further study details as provided by HaEmek Medical Center, Israel:

Biospecimen Retention:   Samples With DNA

Genomic DNA will be isolated from peripheral blood by standard methods. The corresponding intron-exon boundaries of ghrelin and GHSR genes will be analyzed by direct sequencing using the ABI Prism 3100 DNA Analyzer


Estimated Enrollment: 250
Study Start Date: January 2009
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
50 children with GH deficiency
2
50 children with ISS
3
50 children with FTT
4
50 children with obesity
5
50 children without short stature or obesity will serve as controls

Detailed Description:

Background: Obesity, now a global epidemic, is a leading cause of illness and mortality in the developed world. To better understand the pathophysiological mechanisms that underlie weight disorders, increasing attention is being paid to central regulatory elements in energy homeostasis, including food intake and energy expenditure. The human hormone ghrelin is secreted as a preprohormone (preproghrelin), from which two hormones with antagonistic effects are derived: ghrelin, which has orexigenic effects and obestatin, which has anorexigenic effects. Ghrelin's actions are mediated by GH secretagogue receptor (GHSR). Ghrelin synthesis occurs predominantly in epithelial cells of the fundus of the stomach. . As the ligand for GHSR, ghrelin stimulates secretion of GH. In both rodents and humans, ghrelin regulates hunger though its action on hypothalamic feeding centers. Other effects of ghrelin include stimulating gastric emptying, positive effects on cardiovascular function, increasing intestinal peristalsis, and positive exocrine and paracrine pancreatic secretion. Despite its important physiological role, its precise regulatory mechanisms remain ambiguous. Thus, it has been suggested that mutations in ghrelin and its receptor will present clinically with obesity, eating disorders or growth disturbances. To date, only four different mutations have been reported in GHSR and no mutations have been found in the ghrelin gene.

Working hypothesis and aims: We hypothesize that mutations in ghrelin or in its receptor, GHSR, affect appetite regulation and cause growth and eating disorders.

Methods: A total of 250 children followed in the pediatric endocrine department at Ha'Emek Medical Center will be divided into four groups: 50 children with GH deficiency, 50 obese children, 50 children with failure to thrive (FTT),and 50 children with idiopathic short stature (ISS). In addition, 50 children without growth or weight disorders will be included as a control group.

Genomic DNA will be isolated from the peripheral blood by standard methods. The corresponding intron-exon boundaries of the ghrelin and GHSR genes will be analyzed by direct sequencing using an ABI Prism 3100 DNA Analyzer.

Expected results: We anticipate that mutations in ghrelin or its receptor will affect growth and appetite regulation.

Importance: The findings of this study will expand our understanding of ghrelin's role in growth and appetite regulation.

Probable implications for medicine: The development of more specific therapeutic modalities for the treatment of short stature and obesity in children may become possible.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

A total of 250 children followed in the pediatric endocrine department at Ha'Emek Medical Center will be divided into 5 groups: 50 children with GH deficiency,50 obese children, 50 children with failure to thrive (FTT)and 50 children with idiopathic short stature (ISS). 50 children without growth and weight disorders will be included as a control group.

Criteria

Inclusion Criteria:

  • Group1: Children with GH deficiency diagnosed by 2 provocative tests with peak GH less than 10 ng/ml.
  • Group 2:Children with height less than the 3rd centile without any etiology
  • Group 3:children with failure to thrive until the age of 3 years.
  • Group 4: children with obesity defined by BMI above the 90th centile for age and sex.
  • Group 5: children with no endocrine diseases and without obesity or short stature.

Exclusion Criteria:

  • Children with known pediatric or endocrine diseases.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00830141

Contacts
Contact: Yardena Tenenbaum-Rakover, MD 97246495203 rakover_y@clalit.org.il
Contact: Ora Hess, PhD 97246495216

Sponsors and Collaborators
HaEmek Medical Center, Israel
Investigators
Principal Investigator: Yardena Tenenbaum-Rakover, MD Ha"Emek Medical Center, Afula, ISRAEL
  More Information

No publications provided

Responsible Party: Dr Yardena Tenenbaum-Rakover, Ha'Emek Medical Center, Afula, Israel
ClinicalTrials.gov Identifier: NCT00830141     History of Changes
Other Study ID Numbers: 0040-08-EMC
Study First Received: January 25, 2009
Last Updated: January 26, 2009
Health Authority: Israel: Ministry of Health

Keywords provided by HaEmek Medical Center, Israel:
Ghrelin
obesity
idiopathic short stature (ISS)

Additional relevant MeSH terms:
Dwarfism
Obesity
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014