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

NCT ID: NCT01358461

Last Updated: 2017-09-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 240 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2015-05-31

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 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

Conditions

Vagal Syncope

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Patients with vagal syncopes

Patients with vagal syncopes (n=120 : 60 adults \& 60 children)

Blood sampling

Intervention Type: BIOLOGICAL

Blood sampling

ECG-Holter 24 h tape and sino-carotid stimulation test

Intervention Type: 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

Blood sampling

Intervention Type: BIOLOGICAL

Blood sampling

ECG-Holter 24 h tape and sino-carotid stimulation test

Intervention Type: OTHER

ECG-Holter 24 h tape and sino-carotid stimulation test

Interventions

Blood sampling

Blood sampling

Intervention Type: BIOLOGICAL

ECG-Holter 24 h tape and sino-carotid stimulation test

ECG-Holter 24 h tape and sino-carotid stimulation test

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 51 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angelo LIVOLSI

Role: PRINCIPAL_INVESTIGATOR

Hôpitaux Universitaires de Strasbourg

Locations

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Countries

France

Other Identifiers

4900 (2010 - A01451-38)

Identifier Type: -

Identifier Source: org_study_id