Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04257994 |
| Other study ID # |
16.0099 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 15, 2017 |
| Est. completion date |
October 2025 |
Study information
| Verified date |
April 2023 |
| Source |
St. George's Hospital, London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Every week in the UK, 12 apparently healthy and fit individuals under the age of 35 die
suddenly, a tragic event known as sudden cardiac death (SCD). The investigators have shown
that heritable cardiac disorders affect the distribution of proteins at the cardiac cell-cell
junctions, the areas where cardiac cells are mechanically and electrically coupled. This
knowledge has helped the investigators diagnose specific heart disorders in individuals thus
reducing the risk and incidence of SCD. Yet, the primary material required is a heart sample.
A heart biopsy is an invasive process that comes with risks and is not performed unless
absolutely necessary. And it is impossible to obtain a heart sample from an individual that
may be carrying a disease-causing mutation (and hence be at risk of SCD) but does not yet
show evidence of disease manifestation. The investigators recently showed that buccal cells
show changes in protein distribution equivalent to those exhibited by the heart,hence
providing them with a surrogate tissue for the myocardium. The investigators aim to use
buccal smears as a means to identify those at risk of SCD. Patients regularly seen at the
cardiology clinics at St. George's Hospital can participate in the study. The investigators
shall take a buccal smear simply by rubbing a soft brush at the inside of their cheek and
smearing it on a slide. Most individuals willing to participate in the study will only have
to provide the investigators with a sample once. However, in selected cases (for instance, if
the patients show disease progression or have a change in medication) they may be asked to
provide the investigators with a subsequent sample during one of their scheduled follow-up
visits. The process takes only a few seconds, is totally risk- and pain-free and it is
anticipated to have great implications in diagnosis and patient management.
Description:
Exfoliated buccal mucosa cells have been used as a source of material for various genetic
tests and in studies of oral cancer but their use in studies of cardiovascular disease has
been limited. Previous applications have included analysis of telomere length in buccal cells
from patients with ischemic heart failure and measurements of intracellular magnesium levels
in patients undergoing radiofrequency catheter ablation for atrial fibrillation. To the best
of the investigators' knowledge, their study published at Circulation Arrhythmia and
Electrophysiology 9(2) in 2016, was the first analysis of buccal mucosa cells in patients
with a heritable form of heart disease. This analysis included 39 patients diagnosed with
arrhythmogenic cardiomyopathy (ACM), a primary myocardial disease characterized by an
unusually high burden of arrhythmias and sudden cardiac death as well as 15 carriers of
disease-causing mutations without overt disease manifestation. In a subsequent analysis
(unpublished data), 55 additional individuals affected by ACM were sampled and the positive
predictive value of our approach in diagnosing the disease was 91.9%. Although highly
arrhythmogenic, ACM is a relatively rare disorder. The investigators are now at a position to
apply this simple, totally risk-free approach to help identify those individuals at risk of
SCD due to more common forms of heritable arrhythmic disorders including the cardiac
channelopathies. The cardiologists at St. George's University of London evaluate more than
100 families of SCD victims per year for diagnosis and risk assessment. The large number of
individuals evaluated at this single site provides the unprecedented opportunity to use this
novel diagnostic approach to aid significant numbers of those at risk of developing
life-threatening arrhythmias. There are no risks or potential discomfort associated with the
study for the volunteer participants. The outcomes, however, may prove highly beneficial for
prevention of SCD, timely and accurate diagnosis and management of arrhythmic disorders.
The study participants will just be asked to open their mouth. A study team member will rub a
soft brush a few times at the inside of their cheek and smear the brush on a microscopy
slide. The slide will be sprayed with 70% ethanol to preserve the material and taken to the
research laboratory where it will be subjected to immunostaining to study the distribution of
key proteins. The patient will have a total of 4 smears taken (2 from each cheek). For the
majority of the patients, only a single sampling will be enough which will take place during
one of their regular follow-up appointments at the cardiology clinic. There is no pain and no
discomfort associated with the procedure and it lasts only a few seconds. In selected cases,
however, if for instance the investigators want to use the buccal smear to evaluate the
effect of a novel drug treatment on protein distribution, the patient might be asked to
provide the study team with another sample, again during one of his scheduled regular
follow-up visits
