Clinical trial NCT03621007: An Observational,Prospective Natural History Study of Early-Onset Extreme Obesity Due to Bi-Allelic Loss-of-Function Mutations in the POMC, PCSK1 or LEPR Genes
Official title: An Observational,Prospective Natural History Study of Early-Onset Extreme Obesity Due to Bi-Allelic Loss-of-Function Mutations in the POMC, PCSK1 or LEPR Genes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: POMC Deficiency Obesity
PCSK1 Deficiency Obesity
LEPR Deficiency Obesity
Keywords: POMC
LEPR
PCSK1
Bi-Allelic Loss
Obesity
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-08
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with POMC, PCSK1 or LEPR deficiency obesity due to a bi-allelic loss of function genetic mutation will be enrolled in this study.

Brief summary: This is an observational study. There are no protocol-defined visits, although patients are expected to have routine office visits approximately every 6 months. Upon signing of informed consent/assent and study enrollment, historical data will be abstracted from the patient's medical chart. The patient will then be observed prospectively for up to 5 years, with additional data collected from routine healthcare encounters and direct-to-patient questionnaires (where local laws allow), including laboratory tests, physical exam and patient reported outcomes/quality of life measures. Patients will be consented/assented to provide blood samples for biomarker assessments, DNA sequencing and archiving.


Eligibility criteria: Inclusion Criteria:

1. Age 2 years 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. Have documented results of DNA sequencing for the three genes of interest: POMC, PCSK1 and LEPR.
4. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC or PCSK1 genes, resulting in a severe POMC deficiency obesity clinical phenotype, or a similar bi-allelic gene status for the LEPR gene leading to identified LEPR deficiency obesity.
5. Patients who are willing to come in for routine office visits approximately every 6 months.

Exclusion Criteria:

1. Participation within the past 3 months in a clinical trial of any investigational medicine for obesity.
2. Confirmed diagnosis of Prader-Willi syndrome, Bardet-Biedl syndrome, Alström syndrome, or other syndromic form of genetic obesity.

Primary outcomes:
measure: Demographics
timeFrame: Baseline
measure: Medical history
timeFrame: 5 years
measure: Clinical course
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Balçova
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Bornova
country: Turkey
facility: Ege University School of Medicine of Pediatric Endocrinology
city: Istanbul
country: Turkey
facility: Pediatric Endocrinology and Diabetes Marmara University Hospital
Study officials:
affiliation: Rhythm Pharmceuticals, Inc
name: Murray Stewart, MD
role: STUDY_CHAIR
References: