Clinical trial NCT02602769: Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome
Official title: Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Childhood Obesity
Morbid Obesity
Keywords: Hypoventilation syndrome
Hypothalamic dysfunction
Autonomic dysregulation
Rapid onsey obesity
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2015-11-11
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children diagnosed with ROHHAD (Rapid onset Obesity, Hypoventilation, Hypothalamic dysfunction, Autonomic Disturbances), and their first degree relatives.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* Children with ROHHAD syndrome

Exclusion Criteria:

* Children with known genetic causes of obesity

Primary outcomes:
measure: Changes in the transcriptome profile of hypothalamic cells of children with ROHHAD syndrome compared to their unaffected first degree relatives.
timeFrame: 2 year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Vidhu Thaker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.