The Response To Ajmaline Provocation in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT02933437
• Recruitment Status: Unknown
• First Posted: October 14, 2016
• Last Update Posted: November 5, 2019
• Sponsor: St George's, University of London
• Information provided by (Responsible Party): St George's, University of London

Study Description

Brief Summary:

Standard, high lead and sodium channel provoked electrocardiograms of a healthy volunteers will be performed to observe the various ECG changes. Participants will the undergo detailed imaging with cardiac magnetic resonance imaging and deep genotyping to identify structural or genetic variants which might dictate the electrocardiographic patterns at rest and with sodium channel provocation.

Condition or disease	Intervention/treatment	Phase
Brugada Syndrome; Sudden Death	Drug: Ajmaline	Phase 2

Detailed Description:

The investigators will recruit healthy subjects without a history of cardiac symptoms or a family history of sudden death or premature arrhythmogenic cardiac disease. Participants will undergo electrocardiographic phenotype assessment with standard and high lead electrocardiogram and sodium channel provocation. Detailed cardiac structural examination will be performed with cardiac magnetic resonance imaging to look for any variation in mainly right ventricular outflow tract structure and myocardial architecture. Participants will also undergo targeted genomic sequencing to look for variations in genes encoding for cardiac sodium channel.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: An Observational Study Into the Variety of Electrocardiographic Responses to an Ajmaline Provocation in a Healthy Subjects. What Are the Genetic and Structural Variations Dictating This Response ?
• Actual Study Start Date: October 22, 2017
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Healthy Volunteers; Once screened by the investigators, the participants will undergo ajmaline provocation, cardiac magnetic resonance imaging and genotype evaluation	Drug: Ajmaline; Ajmaline 1milligram/kilogram max dose as bolus intravenous over 10 minutes with continuous ECG monitoring; Other Name: GILURYTMAL

Outcome Measures

Primary Outcome Measures :

1. The qualitative and quantitative effects of ajmaline provocation on parameters of cardiac conduction in healthy subjects using the surface electrocardiogram [ Time Frame: ten minutes ]
   The investigators will be undertaking quantitative analysis of the changes in cardiac conduction observed in the presence of ajmaline. This is measured in time intervals in milliseconds (ms) and magnitude of electrical conduction which will be expressed in millivolts (mv), but can also be expressed in millimetres (mm). The investigators will use the latter to quantify area changes which will be expressed as millimetres squared (mm2). A quantitive description of the electrocardiographic patterns observed will also be performed in addition to further qualitative analysis of vectors created by the variety of ECG morphologies observed, this geometrical assessment will be measured in degrees. As this is a cohort of healthy volunteers the variations observed are anticipated to be part of the "normal" variation, therefore the statistical analysis of these findings will be as a cohort not individual.

Secondary Outcome Measures :

1. The influence of normal variations in right ventricular outflow tract dimensions on the electrocardiographic response to ajmaline provocation in healthy subjects using cardiac magnetic resonance imaging. [ Time Frame: intraoperative ]
   Using existing cardiac magnetic resonance imaging modality, cardiac dimensions will be measured in millimetres (mm). This includes wall thickness and internal cavity size. Additionally volumetric assessment for chamber size will be made using millilitres (ml), this allows for a 3 dimensional appreciation. Using contrast agents, an assessment of the composition of cardiac muscle can be made and can identify the presence or absence of "myocardial fibrosis,"as a binary outcome measure. Further methods will be used to quantify the degree of fibrosis if observed, this will be expressed as a percentage (%) area of fibrosis divided by total area of myocardium multiplied by 100. The location of this fibrosis within the heart will also be noted.
2. Genotype linkage analysis of the electrocardiographic response to ajmaline provocation in healthy subjects using candidate gene and gene wide association studies. [ Time Frame: through study completion, an average of 2 years ]
   Targeted genetic sequencing of the sodium channel genes SCN5A and SCN10A and gene wide association studies for rare variations

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Asymptomatic healthy Volunteers

Exclusion Criteria:

• • Any prior cardiovascular illness

  • Previous cardiac symptoms.
  • History of unexplained syncope
  • Any family history of proven sudden cardiac death or unexplained sudden death either in adulthood or infancy.
  • Those unable to provide a two generation family history
  • Abnormal resting ECG
  • Any contraindications to cardiac magnetic resonance imaging
  • Pregnant or breastfeeding women
  • Intercurrent use of any medication known to be contraindicated in Brugada Syndrome

Contacts and Locations

Locations

United Kingdom

St George's University Of London

London, United Kingdom

Sponsors and Collaborators

St George's, University of London

Investigators

• Principal Investigator: Elijah Behr, MD; St George's, University of London

More Information

• Responsible Party: St George's, University of London
• ClinicalTrials.gov Identifier: NCT02933437
• Other Study ID Numbers: 16.0012; 2016-004277-41 ( EudraCT Number )
• First Posted: October 14, 2016
• Last Update Posted: November 5, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St George's, University of London:

Brugada syndrome; SCN5A; SCN10A; Ajmaline

Additional relevant MeSH terms:

Brugada Syndrome; Death, Sudden; Pathologic Processes; Death; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Genetic Diseases, Inborn; Ajmaline; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action