Ignite Creation Date:
2024-05-05 @ 11:33 PM
Last Modification Date:
2024-10-26 @ 10:35 AM
Study NCT ID:
NCT01358461
Status:
COMPLETED
Last Update Posted:
2017-09-08
First Post:
2011-05-20
Brief Title:
Validation of a Non Invasive Blood Marker of SIDS and Vagal Disorders
Sponsor:
University Hospital Strasbourg France
Organization:
University Hospital Strasbourg France
Study Overview
Official Title:
Circulating Biomarkers of Muscarinic Receptor Overexpression and Vagal Disorders
Status:
COMPLETED
Status Verified Date:
2017-09
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:
Context
The investigators recently demonstrated a highly significant increase in muscarinic receptor density in the myocardium of infants deceased from sudden infant death syndrome SIDS compared to those of infants deceased from identified causes 1 Muscarinic receptor overexpression was found in all SIDS samples studied to date It was associated with an average increase in acetylcholinesterase activity appearing as a compensatory mechanism to oppose the cardiac muscarinic receptor overexpression Similar vago-cardiac abnormalities were detected in a rabbit model of vagal hyperreactivity that the investigators first described some years ago2 In these hyperreactive animals expression of muscarinic receptors was also enhanced in blood white cells Noticeably the pattern of changes in these cells paralleled the pattern of changes in the heart Thus muscarinic abnormalities in cardiac tissues could be inferred with high confidence from those measured in lymphocytesThis was the first report of a vago-cardiac abnormality in sudden infant death syndrome The investigators findings also provided original and important perspectives for the identification and therapeutic management of infants at risk of sudden death As such the publication of the investigators work raised a major interest from the population and from the scientific and medical communities in particular cardio-pediatricians ObjectivesThe objective of the present clinical project is to validate in human lymphocytes muscarinic receptor expression level assessed by quantitative RT-PCR as a circulating biomarker of autonomic nervous system dysfunction and more specifically of vagal hyperactivity and of risk of sudden death The project will include 2 major items conducted in parallel1 evaluation of the muscarinic receptor expression in lymphocytes from adults with vagal syncopes n60 patients from an existing file versus 60 controls Cardiology unit Clinical Investigation Centre CIC Laboratory of Neurobiology and Cardiovascular Pharmacology 2 evaluation of the muscarinic receptor expression in lymphocytes from children with vagal syncopes n60 versus 60 controls Pediatry unit Clinical Investigation Centre Laboratory of Neurobiology and Cardiovascular PharmacologyPerspectivesThis project represents the first step of validation of a circulating marker of vagal hyperactivity and of risk of SIDS in human Once this step is completed the investigators will start with the prospective study muscarinic receptor expression in lymphocytes and SIDS cord blood collected at birth and follow up of the new-borns Maternity ward CIC Laboratory of Neurobiology and Cardiovascular Pharmacology Then therapeutic preventive management becomes a realistic objective A therapeutic clinical study will then be started with atropinic drugs in order to test their potential protective action against sudden death The final objective of the investigators research is the prevention of SIDS through i identification - as soon as birth - of new-borns at high risk and ii appropriate prophylactic therapy The investigators work also opens exciting perspectives in the field of the still poorly understood vagal disorders in children and adults such as vagal pauses1 Livolsi et coll Plos One 5 e9464 2010 2 Livolsi et coll Circulation 106 2301-2304 2002
The investigators recently demonstrated a highly significant increase in muscarinic receptor density in the myocardium of infants deceased from sudden infant death syndrome SIDS compared to those of infants deceased from identified causes 1 Muscarinic receptor overexpression was found in all SIDS samples studied to date It was associated with an average increase in acetylcholinesterase activity appearing as a compensatory mechanism to oppose the cardiac muscarinic receptor overexpression Similar vago-cardiac abnormalities were detected in a rabbit model of vagal hyperreactivity that the investigators first described some years ago2 In these hyperreactive animals expression of muscarinic receptors was also enhanced in blood white cells Noticeably the pattern of changes in these cells paralleled the pattern of changes in the heart Thus muscarinic abnormalities in cardiac tissues could be inferred with high confidence from those measured in lymphocytesThis was the first report of a vago-cardiac abnormality in sudden infant death syndrome The investigators findings also provided original and important perspectives for the identification and therapeutic management of infants at risk of sudden death As such the publication of the investigators work raised a major interest from the population and from the scientific and medical communities in particular cardio-pediatricians ObjectivesThe objective of the present clinical project is to validate in human lymphocytes muscarinic receptor expression level assessed by quantitative RT-PCR as a circulating biomarker of autonomic nervous system dysfunction and more specifically of vagal hyperactivity and of risk of sudden death The project will include 2 major items conducted in parallel1 evaluation of the muscarinic receptor expression in lymphocytes from adults with vagal syncopes n60 patients from an existing file versus 60 controls Cardiology unit Clinical Investigation Centre CIC Laboratory of Neurobiology and Cardiovascular Pharmacology 2 evaluation of the muscarinic receptor expression in lymphocytes from children with vagal syncopes n60 versus 60 controls Pediatry unit Clinical Investigation Centre Laboratory of Neurobiology and Cardiovascular PharmacologyPerspectivesThis project represents the first step of validation of a circulating marker of vagal hyperactivity and of risk of SIDS in human Once this step is completed the investigators will start with the prospective study muscarinic receptor expression in lymphocytes and SIDS cord blood collected at birth and follow up of the new-borns Maternity ward CIC Laboratory of Neurobiology and Cardiovascular Pharmacology Then therapeutic preventive management becomes a realistic objective A therapeutic clinical study will then be started with atropinic drugs in order to test their potential protective action against sudden death The final objective of the investigators research is the prevention of SIDS through i identification - as soon as birth - of new-borns at high risk and ii appropriate prophylactic therapy The investigators work also opens exciting perspectives in the field of the still poorly understood vagal disorders in children and adults such as vagal pauses1 Livolsi et coll Plos One 5 e9464 2010 2 Livolsi et coll Circulation 106 2301-2304 2002
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None