Clinical trial NCT02849977: Genetic Testing and Phenotypic Characterization of Severely Obese Pediatric and Adult Volunteers
Official title: Genetic Testing and Phenotypic Characterization of Severely Obese Pediatric and Adult Volunteers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pro-opiomelanocortin (POMC), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1) and Leptin Receptor (LepR) Gene Mutations
Keywords: POMC
PCSK1
Pro-opiomelanocortin
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-29
Enrollment: 5966
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The objective is to identify individuals with severe, early onset morbid obesity (EOMO), who are aged 2 years of age or older, and are suspected to be either homozygous, compound heterozygous or heterozygous for loss of function mutations in the POMC, PCSK1 or LepR gene, leading to a clinical presentation of Melanocortin 4 (MC4) pathway deficiency obesity. Individuals may be contacted for further assessment of clinical features (including questionnaires on past weight and medical history and current hunger and feeding behavior symptoms) and/or participation in future Rhythm clinical trials.

Brief summary: The purpose of this screening study is to identify people who have a rare genetic cause of obesity - specifically three genetic variants (a change in the DNA structure) of the POMC, PCSK1 and LepR genes that are currently known to result in obesity.

This screening study will not include any investigational drugs. You will be asked to provide a DNA sample and answer some questions about your medical history and hunger.


Eligibility criteria: Individuals who meet any of the following inclusion criteria may be eligible:

1. Participant aged 2 or older.
2. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent/assent.
3. ≥40kg/m2 (age 18 and older) or 1.4x 95th percentile of BMI for age (ages 2-17) - with evidence of hunger or hyperphagia by screening surveys, indicated by a patient or observer score at or greater than midpoint of scale.

   o Individuals with clinical evidence of RGDO (per appendix 4) but do not meet the BMI criteria may be included if the investigators estimation and proband demonstrates a BMI Z-score difference of \>1 between proband and any other sibling; and/or the proband demonstrates a BMI difference \>10 kg/m2 between proband and parents.
4. ≥50 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17). Cohorts included under this criteria include ≥50-60 kg/m2 (age 18 and older) or 1.5x 95th percentile of BMI for age (ages 2-17) and ≥60 kg/m2 (age 18 and older) or 1.6x 95th percentile of BMI for age (ages 2-17).
5. ≥ 40 kg/m2 (pre-operative) or 1.4x 95th percentile of BMI for age (ages 12-17) with history of bariatric surgery or planned surgery within 3 months (prior to or following screening).

Individuals who meet any of the following exclusion criteria will not be eligible:

1. Prior craniopharyngioma or other hypothalamic brain region surgery or surgeries/procedures for brain tumor, i.e., ventriculoperitoneal shunt and radiation therapy
2. Diagnosis of Prader-Willi syndrome

Primary outcomes:
measure: Identification of individuals with POMC, LepR or PCSK1 genetic mutations
timeFrame: 1 Year
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - Phoenix Southeast
state: Arizona
city: Mesa
country: United States
facility: Clinical Research Advantage Inc.
state: Arizona
city: Tucson
country: United States
facility: Tucson Neuroscience Research - M3 Wake Research
state: Arizona
city: Encino
country: United States
state: California
city: Los Alamitos
country: United States
facility: PRI, LLC - Los Alamitos - M3 Wake Research
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trails
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Newport Beach
country: United States
facility: PRI, LLC - Newport Beach - M3 Wake Research
state: California
city: Wilmington
country: United States
facility: Nemours Foundation Alfred Dupont Children's Hospital
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hialeah
country: United States
facility: South Florida Clinical Trials
state: Florida
city: Orlando
country: United States
facility: Translational Research Inst. for Metabolism and Diabetes
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Palm Harbor
country: United States
facility: Palm Harbor Medical Associates - BTC - PPDS
state: Florida
city: Pinellas Park
country: United States
facility: Synexus Clinical Research US, Inc. - St. Petersburg
state: Florida
city: Chicago
country: United States
facility: Synexus Clinical Research US, Inc. - Chicago
state: Illinois
city: Portland
country: United States
facility: Maine Medical Partners Pediatric Specialty Care
state: Maine
city: Springfield
country: United States
facility: Baystate Children's Hospital, Division of Pediatric Endocrinology
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital Healthy Weight Center
state: Michigan
city: Bridgeton
country: United States
facility: Synexus Clinical Research US, Inc. - West Florissant Internists
state: Missouri
city: Las Vegas
country: United States
facility: Impact Clinical Trials - Las Vegas
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Brooklyn
country: United States
facility: New York Clinical Trials-Brooklyn
state: New York
city: Buffalo
country: United States
facility: Division of Endocrinology/Diabetes Amanda House
state: New York
city: Lake Success
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: New York Clinical Trials-Manhattan
state: New York
city: Chapel Hill
country: United States
facility: UNC Health Care - NC Children's Specialty Clinic
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Akron
country: United States
facility: Synexus Clinical Research US, Inc. - Akron
state: Ohio
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital, Center for Healthy Weight and Nutrition
state: Ohio
city: Columbus
country: United States
facility: Synexus Clinical Research US, Inc. - Columbus
state: Ohio
city: Oklahoma City
country: United States
facility: Synexus Clinical Research US, Inc. - Centennial Health, PC -
state: Oklahoma
city: Anderson
country: United States
facility: Synexus Clinical Research US, Inc. - Primary Care Associates
state: South Carolina
city: Memphis
country: United States
facility: University of Tennesseee Health Science Center
state: Tennessee
city: Memphis
country: United States
facility: Medical Research Center of Memphis, LLC - M3 Wake Research
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Dallas
country: United States
facility: Synexus - Synexus US, LP - Dallas
state: Texas
city: DeSoto
country: United States
facility: Global Medical Research - M3 Wake Research
state: Texas
city: San Antonio
country: United States
facility: Synexus Clinical Research US, Inc. - San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Department of Surgery
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Berlin
country: Germany
facility: Charite Campus Virchow-Klinikum Institute for Experimental Pediatric Endocrinology
city: Patras
country: Greece
facility: University of Hospital of Patras
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel - Petah Tikvah - PIN
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - PPDS
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Oggebbio
country: Italy
facility: IRCCS Istituto Auxologico Italiano
city: Guimarães
country: Portugal
facility: Hospital Senhora da Oliveira -Guimaraes, E.P.E
Study officials:
affiliation: Rhythm Pharmceuticals, Inc.
name: David Meeker
role: STUDY_CHAIR
References: