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Recruiting NCT02602769

Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome

— Observational Childhood Obesity Morbid Obesity

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Transcriptome profiling.
Who it may be relevant to
Registry conditions: Childhood Obesity, Morbid Obesity. Basic parameters: 2 years — 20 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Detailed 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.

Interventions

  • 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.

Primary outcome measures

  • Changes in the transcriptome profile of hypothalamic cells of children with ROHHAD syndrome compared to their unaffected first degree relatives. [Time frame: 2 year]

Eligibility criteria

Inclusion criteria

  • Children with ROHHAD syndrome

Exclusion criteria

  • Children with known genetic causes of obesity

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model
Case-control

Study locations

United States · 2 centers
  • Boston Children's Hospital — Boston
  • Columbia University Irving Medical Center — New York

Publications

  • 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. 2015 May;100(5):1723-30. doi: 10.1210/jc.2014-4215. Epub 2015 Mar 17. PMID 25781356

Identifiers

NCT: NCT02602769 · AAAS4650 · P00018387 · R21DK129893

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗