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The Response To Ajmaline Provocation in Healthy Subjects

Primary Purpose

Brugada Syndrome, Sudden Death

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Ajmaline
Sponsored by
St George's, University of London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Brugada Syndrome focused on measuring Brugada syndrome, SCN5A, SCN10A, Ajmaline

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • St George's University Of London

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Healthy Volunteers

Arm Description

Once screened by the investigators, the participants will undergo ajmaline provocation, cardiac magnetic resonance imaging and genotype evaluation

Outcomes

Primary Outcome Measures

The qualitative and quantitative effects of ajmaline provocation on parameters of cardiac conduction in healthy subjects using the surface electrocardiogram
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

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.
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.
Genotype linkage analysis of the electrocardiographic response to ajmaline provocation in healthy subjects using candidate gene and gene wide association studies.
Targeted genetic sequencing of the sodium channel genes SCN5A and SCN10A and gene wide association studies for rare variations

Full Information

First Posted
August 31, 2016
Last Updated
November 4, 2019
Sponsor
St George's, University of London
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1. Study Identification

Unique Protocol Identification Number
NCT02933437
Brief Title
The Response To Ajmaline Provocation in Healthy Subjects
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 ?
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 22, 2017 (Actual)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St George's, University of London

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brugada Syndrome, Sudden Death
Keywords
Brugada syndrome, SCN5A, SCN10A, Ajmaline

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Healthy Volunteers
Arm Type
Experimental
Arm Description
Once screened by the investigators, the participants will undergo ajmaline provocation, cardiac magnetic resonance imaging and genotype evaluation
Intervention Type
Drug
Intervention Name(s)
Ajmaline
Other Intervention Name(s)
GILURYTMAL
Intervention Description
Ajmaline 1milligram/kilogram max dose as bolus intravenous over 10 minutes with continuous ECG monitoring
Primary Outcome Measure Information:
Title
The qualitative and quantitative effects of ajmaline provocation on parameters of cardiac conduction in healthy subjects using the surface electrocardiogram
Description
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.
Time Frame
ten minutes
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
intraoperative
Title
Genotype linkage analysis of the electrocardiographic response to ajmaline provocation in healthy subjects using candidate gene and gene wide association studies.
Description
Targeted genetic sequencing of the sodium channel genes SCN5A and SCN10A and gene wide association studies for rare variations
Time Frame
through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elijah Behr, MD
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
St George's University Of London
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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The Response To Ajmaline Provocation in Healthy Subjects

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