Validation of a Non Invasive Blood Marker of SIDS and Vagal Disorders

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by University Hospital, Strasbourg, France.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier:
NCT01358461
First received: May 20, 2011
Last updated: June 14, 2012
Last verified: June 2012

May 20, 2011
June 14, 2012
May 2011
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Complete list of historical versions of study NCT01358461 on ClinicalTrials.gov Archive Site
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Validation of a Non Invasive Blood Marker of SIDS and Vagal Disorders
Circulating Biomarker(s) of Muscarinic Receptor Overexpression and Vagal Disorders.

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 lymphocytes.This 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 parallel:1. evaluation of the muscarinic receptor expression in lymphocytes from adults with vagal syncopes (n=60 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 (n=60 versus 60 controls) (Pediatry unit + Clinical Investigation Centre + Laboratory of Neurobiology and Cardiovascular Pharmacology).PerspectivesThis 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 pauses.1 Livolsi et coll, Plos One 5, e9464, 2010 ; 2 Livolsi et coll, Circulation 106, 2301-2304, 2002

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Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
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Retention:   Samples Without DNA
Description:

Blood

Non-Probability Sample

University Hospital

Vagal Syncope
  • Biological: Blood sampling
    Blood sampling
  • Other: ECG-Holter 24 h tape and sino-carotid stimulation test
    ECG-Holter 24 h tape and sino-carotid stimulation test
  • Patients with vagal syncopes
    Patients with vagal syncopes (n=120 : 60 adults & 60 children)
    Interventions:
    • Biological: Blood sampling
    • Other: ECG-Holter 24 h tape and sino-carotid stimulation test
  • Subjects controls without vagal syncopes
    Subjects controls without vagal syncopes (n=120:60 adults & 60 children
    Interventions:
    • Biological: Blood sampling
    • Other: ECG-Holter 24 h tape and sino-carotid stimulation test
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
240
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Inclusion Criteria:

  • Man or woman aged 1 month to 50 years
  • Patients with clinical signs of recurrent severe vagal syncopes
  • Controls without clinical signs of recurrent severe vagal syncopes
  • Mandatory clinical examination prior to enrolment

Exclusion Criteria:

  • Autonomic nervous system disorders
  • Cardiovascular, neurologic, psychiatric or metabolic diseases
  • Drugs interfering with autonomic nervous system
  • Doping or drug abuse
  • Chronic smoking (more than 3 cigarettes a day
  • Pregnancy
Both
1 Month to 51 Years
Yes
France
 
NCT01358461
4900 (2010 - A01451-38)
No
University Hospital, Strasbourg, France
University Hospital, Strasbourg, France
Not Provided
Principal Investigator: Angelo LIVOLSI Hôpitaux Universitaires de Strasbourg
University Hospital, Strasbourg, France
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP