Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome

NCT ID: NCT02602769

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 12 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2026-12-31

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.

Conditions

Childhood Obesity; Morbid Obesity

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Cases of ROHHAD syndrome

Children diagnosed with ROHHAD syndrome during the course of their clinical care by their physicians.

The investigators will perform transcriptome profiling in this group.

Transcriptome profiling

Intervention Type: DIAGNOSTIC_TEST

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.

Control cohort

Unaffected first degree family members. The investigators will perform transcriptome profiling in this group.

Transcriptome profiling

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Children with ROHHAD syndrome

Exclusion Criteria

• Children with known genetic causes of obesity

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

ROHHAD Association

UNKNOWN

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Vidhu V. Thaker

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vidhu Thaker, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Boston Children's Hospital

Boston, New York, United States

Site Status: COMPLETED

Columbia University Irving Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Vidhu Thaker, MD

Role: CONTACT

vvt2114@cumc.columbia.edu

2128515315

Facility Contacts

Vidhu Thaker, MD

Role: primary

vvt2114@cumc.columbia.edu

212-851-5315

References

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.

Reference Type: RESULT

PMID: 25781356 (View on PubMed)

Other Identifiers

P00018387

Identifier Type: OTHER

Identifier Source: secondary_id

R21DK129893

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAS4650

Identifier Type: -

Identifier Source: org_study_id