Ignite Creation Date:
2024-05-06 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 12:48 PM
Study NCT ID:
NCT03568669
Status:
RECRUITING
Last Update Posted:
2023-08-31
First Post:
2018-06-14
Brief Title:
Neurocognition in Congenital Central Hypoventilation Syndrome CCHS
Sponsor:
Debra Weese-Mayer
Organization:
Ann Robert H Lurie Childrens Hospital of Chicago
Study Overview
Official Title:
Neurocognitive Outcome as a Metric for Evaluating Therapeutic Intervention and Treatment Mechanisms in Congenital Central Hypoventilation Syndrome CCHS A Multi-Site Study Using The NIH Toolbox
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Congenital central hypoventilation syndrome CCHS is a rare disorder of autonomic and respiratory regulation that frequently alters oxygen delivery to the brain In CCHS neurocognitive function has been of great concern because of the potential for repeated hypoxemia and hypercarbia in activities of daily living in addition to hypoventilation with related hypoxemia and hypercarbia during sleep As the worlds leading referral center for CCHS the Center for Autonomic Medicine in Pediatrics CAMP is engaged in ongoing research to identify factors that impact neurocognitive performance in patients with CCHS in order to optimize clinical management and improve long term neurocognitive outcomes
The purpose of this IRB-approved research study is to implement the NIH Toolbox as a standard measurement of cognitive health in patients with CCHS Further the study aims to determine how intrinsic and extrinsic disease factors such as age at diagnosis PHOX2B mutation type and genotype and nature of past and present artificial respiratory intervention affect the NIH Toolbox Cognitive scores of individuals with CCHS Eligible participants will complete a 45-minute NIH Toolbox assessment and parents or adult participants will complete an associated 15-minute Research Electronic Data Capture REDCap questionnaire
The purpose of this IRB-approved research study is to implement the NIH Toolbox as a standard measurement of cognitive health in patients with CCHS Further the study aims to determine how intrinsic and extrinsic disease factors such as age at diagnosis PHOX2B mutation type and genotype and nature of past and present artificial respiratory intervention affect the NIH Toolbox Cognitive scores of individuals with CCHS Eligible participants will complete a 45-minute NIH Toolbox assessment and parents or adult participants will complete an associated 15-minute Research Electronic Data Capture REDCap questionnaire
Detailed Description:
CCHS is a genetic autonomic nervous system disorder caused by heterozygous mutations in the PHOX2B gene 90-92 are caused by polyalanine repeat expansion mutations PARMs with 4 to 13 additional alanines on the affected allele in the 20 alanine repeat region of exon 3 resulting genotype is 2024-2033 The remaining 8-10 of PHOX2B mutations are non-PARMs including missense nonsense frameshift or stop codon mutations And less than 1 of CCHS patients are heterozygous for a large deletion eliminating the entire PHOX2B gene and potentially other neighboring genes Different causative mutations vary in the level of associated protein dysfunction leading to variability in the severity of the CCHS phenotype and potentially in the severity and frequency of resulting neurocognitive insult Severe cyanotic breath-holding spells and prolonged sinus pauses are two phenotypic features of CCHS known to alter regional blood flowoxygen saturation to the brain near-infrared spectroscopy personal communication 2018 The fact that both of these phenotypic presentations are associated with particular PHOX2B genotypes suggests that genetic factors intrinsic to CCHS pathology might influence neurocognitive outcomes
A recent report suggests that a number of extrinsic factors might also affect neurocognitive performance in patients with CCHS with later identification and less than conservative management in terms of artificial ventilation While all cases of CCHS require assisted ventilation during sleep some more severe cases require 24-hourday artificial ventilation Methods of assisted ventilation differ case-by-case and are chosen based on several factors including the patients level of alveolar hypoventilation physician recommendation and a familys ability to provide the recommended support While these mechanisms are all meant to ensure optimal ventilation the level of physiological oxygen stability and the stability of carbon dioxide levels provided with each varies Thus methods of respiratory assistance are likely to influence neurocognitive outcomes
Currently there is no standard mechanism for examining the neurocognitive impact that intrinsic pathology PHOX2B genotype and extrinsic factors age of diagnosis and method of respiratory assistance have on CCHS patients across age groups and between sites In order to establish such a standard this study aims to use a brief and reliable cognitive battery called the NIH Toolbox at multiple sites The NIH Toolbox was developed to standardize evaluations in specific clinical populations for investigations of neurological development and change disease recovery and therapeutic interventions The Toolbox consists of a series of cognitive assessments of executive function attention memory and language designed for broad use across age groups from childhood to adulthood
Participants in this study will initially be recruited during clinical visits at the Ann Robert H Lurie Childrens Hospital of Chicago Seattle Childrens Hospital and Childrens Hospital Los Angeles as well as at meetings of the CCHS Family Network All participants will complete a 45-minute NIH Toolbox cognitive assessment that is administered on an iPad by trained study staff Additionally parents or adult participants will complete a simple 15-minute electronic REDCap questionnaire designed to obtain basic information including PHOX2B genotype age of CCHS diagnosis past and present artificial ventilation interface example mask tracheostomy etc past and present mode of artificial ventilation positive pressure ventilator negative pressure ventilator phrenic nerve-diaphragm pacers phenotype and disease history After initial participation study subjects will complete the Toolbox and questionnaire at annual clinic visits or potentially at CCHS Family Network meetings to allow for longitudinal data collection
The study will validate the NIH Toolbox as an assessment of cognitive performance and longitudinal cognitive outcomes in CCHS patients Additionally the study will characterize the effect of intrinsic and extrinsic disease factors on the neurocognitive outcomes of affected individuals in order optimize care for CCHS patients
A recent report suggests that a number of extrinsic factors might also affect neurocognitive performance in patients with CCHS with later identification and less than conservative management in terms of artificial ventilation While all cases of CCHS require assisted ventilation during sleep some more severe cases require 24-hourday artificial ventilation Methods of assisted ventilation differ case-by-case and are chosen based on several factors including the patients level of alveolar hypoventilation physician recommendation and a familys ability to provide the recommended support While these mechanisms are all meant to ensure optimal ventilation the level of physiological oxygen stability and the stability of carbon dioxide levels provided with each varies Thus methods of respiratory assistance are likely to influence neurocognitive outcomes
Currently there is no standard mechanism for examining the neurocognitive impact that intrinsic pathology PHOX2B genotype and extrinsic factors age of diagnosis and method of respiratory assistance have on CCHS patients across age groups and between sites In order to establish such a standard this study aims to use a brief and reliable cognitive battery called the NIH Toolbox at multiple sites The NIH Toolbox was developed to standardize evaluations in specific clinical populations for investigations of neurological development and change disease recovery and therapeutic interventions The Toolbox consists of a series of cognitive assessments of executive function attention memory and language designed for broad use across age groups from childhood to adulthood
Participants in this study will initially be recruited during clinical visits at the Ann Robert H Lurie Childrens Hospital of Chicago Seattle Childrens Hospital and Childrens Hospital Los Angeles as well as at meetings of the CCHS Family Network All participants will complete a 45-minute NIH Toolbox cognitive assessment that is administered on an iPad by trained study staff Additionally parents or adult participants will complete a simple 15-minute electronic REDCap questionnaire designed to obtain basic information including PHOX2B genotype age of CCHS diagnosis past and present artificial ventilation interface example mask tracheostomy etc past and present mode of artificial ventilation positive pressure ventilator negative pressure ventilator phrenic nerve-diaphragm pacers phenotype and disease history After initial participation study subjects will complete the Toolbox and questionnaire at annual clinic visits or potentially at CCHS Family Network meetings to allow for longitudinal data collection
The study will validate the NIH Toolbox as an assessment of cognitive performance and longitudinal cognitive outcomes in CCHS patients Additionally the study will characterize the effect of intrinsic and extrinsic disease factors on the neurocognitive outcomes of affected individuals in order optimize care for CCHS patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None