Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome

Morbid Obesity Clinical Trial

Official title:

Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02602769
• Other study ID #: AAAS4650
• Secondary ID: P00018387
• Status: Recruiting
• Start date: November 2015
• Est. completion date: December 2025

Study information

• Verified date: August 2023
• Source: Columbia University
• Contact: Vidhu Thaker, MD
• Phone: 2128515315
• Email: vvt2114[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Rapid onset Obesity, Hypoventilation, Hypothalamic dysfunction and Autonomic Dysregulation (ROHHAD) is a syndrome named in 2007. The hallmark of the syndrome is the rapid onset obesity and dysregulation of central ventilation. There is little information about the metabolic changes that lead to the rapid onset obesity in these children. The investigators would like to study the metabolic phenotype of these children to understand the disturbances in energy balance that lead to the rapid onset obesity.

Description:

Late-onset hypoventilation syndrome with hypothalamic dysfunction was first described in 1965 and renamed to ROHHAD syndrome in 2007 by Ize-Ludlow et al.

The hallmark of ROHHAD syndrome is rapid-onset obesity starting at approximately 1.5 years of age with weight gain of 12-20 kg/year, central hypoventilation distinct from the obstructive hypoventilation caused by obesity, hyperphagia, a spectrum of pituitary hormonal dysfunction, and autonomic disturbances including temperature, blood pressure, and nociception abnormalities. Some children have been noted with developmental and behavioral abnormalities. Tumors of neural crest origin have been identified in 25-33% of the patients. The etiology of ROHHAD syndrome and the cause of rapid onset obesity is unknown.

The aims of this study are to understand the whole transcriptome profiling of patient specific induced pluripotent cell (iPSC) derived hypothalamic neurons to understand the transcriptional level changes that give rise to the manifestations seen in ROHHAD syndrome.

Aim 1. Generate patient specific iPSC-derived hypothalamic neurons from children with ROHHAD syndrome and their unaffected first degree relatives.

Aim 2: Compare the whole transcriptome profiling of the patient derived cells compared to those of unaffected relatives and reference datasets to understand the differences in transcriptome that gives rise to ROHHAD syndrome.

Aim 3: Selected patients may be invited to participate for detailed metabolic phenotyping to understand the mechanisms of excessive weight gain.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 20 Years

Eligibility

Inclusion Criteria:

• Children with ROHHAD syndrome

Exclusion Criteria:

• Children with known genetic causes of obesity

Related Conditions & MeSH terms

• Childhood Obesity
• Morbid Obesity
• Obesity
• Obesity, Morbid
• Pediatric Obesity

Intervention

Diagnostic Test:
• Transcriptome profiling
The investigators will obtain blood to extract peripheral mononuclear cells. These cells will be used to generate patient specific hypothalamic cells that will be used for transcriptome profiling.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	New York
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Thaker VV, Esteves KM, Towne MC, Brownstein CA, James PM, Crowley L, Hirschhorn JN, Elsea SH, Beggs AH, Picker J, Agrawal PB. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the transcriptome profile of hypothalamic cells of children with ROHHAD syndrome compared to their unaffected first degree relatives.	The investigators will perform whole transcriptome profiling of iPSC-derived hypothalamic neurons and compare the whole genome sequencing to identify the changes that may give rise to the disease.	2 year