- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04257994
Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
Analysis of Distribution of Cell-cell Junction Proteins in Buccal Smear Samples From Patients With Arrhythmic Disorders and Family Members at Risk as a Means for Diagnosis
Study Overview
Status
Intervention / Treatment
Detailed 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 In a subsequent analysis (unpublished data), 55 additional individuals affected by ACM were sampled and the positive predictive value of our approach in diagnosing the disease was 91.9%.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
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, SW17 0RE
- St George's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:• Participants will include patients diagnosed with a heritable arrhythmic disorder (including arrhythmogenic, hypertrophic and dilated cardiomyopathy, cardiac sarcoidosis as well as cardiac channelopathies; Long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) followed at the Inherited Cardiac Conditions (ICC) service of St. George's University Hospitals NHS Foundation Trust.
- Family members of victims of SCD evaluated at the same clinic for risk assessment and diagnosis. These groups include both individuals with clear disease manifestation (termed "affected") as shown by conventional diagnostic approaches (electrocardiography, echocardiography, cardiac MRI, Holter monitoring) as well as potential carriers of disease-causing mutations who, however, may not/not yet manifest any overt sign of cardiovascular abnormalities (termed "carriers"). These are typically family members of probands diagnosed with a heritable arrhythmic disorder or family members of a sudden cardiac death victim.
- All individuals that fall in the above categories will be included regardless of their management (medication, devices, and surgical procedures).
- Individuals with co-existing conditions will also be included and their medical history will be taken into account when interpreting the results of the immunohistochemical analysis.
- Adult individuals (>18 years of age).
- Pregnant women will be included as the approach used is not in any way harmful or uncomfortable.
- All individuals must have provided the study team with a signed informed consent in order to participate in the study.
Exclusion Criteria:• Children under 18 years of age
- Individuals lacking decisional capacity.
- Individuals with non-heritable, non-arrhythmic cardiac disorders (such as ischemic heart disease or inflammatory disorders) followed at St. George's University Hospitals NHS Foundation Trust.
- Non-English speakers will be excluded from the study unless a translator is present who can thoroughly explain to them the research question/plan in order for them to provide an informed consent.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
patients with arrhythmic disorders
Participants will include patients diagnosed with a heritable arrhythmic disorder (including arrhythmogenic, hypertrophic and dilated cardiomyopathy, cardiac sarcoidosis as well as cardiac channelopathies; Long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) followed at the Inherited Cardiac Conditions (ICC) service of St. George's University Hospitals NHS Foundation Trust as well as family members of victims of SCD evaluated at the same clinic for risk assessment and diagnosis.
|
A sample will be taken from the inside of the participants' cheeks using a soft brush
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
alteration of protein distribution in arrhythmic disorders
Time Frame: 4 years
|
The primary outcome of the study is to evaluate if specific heritable arrhythmic disorders are associated with changes in selected protein distribution at cell-cell junctions within the buccal mucosa.
The investigators' preliminary studies suggest that protein distribution alterations in the buccal mucosa mirror equivalent changes that occur in the myocardium of patients with ACM.
This study will evaluate the use of this "novel diagnostic tool" in individuals at risk of sudden cardiac death due to other, more common forms of arrhythmic disorders.
The processing approach (laboratory technique: immunocytochemistry) for protein visualization has been optimized to be qualitative rather than quantitative.
In this sense - each sample will be characterized by "presence" or "absence" of a specific protein at the cell-cell connections.
The investigators deem that the qualitative approach is not subject to bias and will ensure accuracy and reproducibility of the results.
|
4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
correlation of protein distribution with participants' genotype
Time Frame: 4 years
|
A potential secondary outcome of the research is whether the investigators can correlate protein distribution in the buccal mucosa with specific genotypes.
The investigators' preliminary results on the cohort of patients with ACM suggest that mutations in different genes result in different protein distribution patterns within the buccal mucosa.
Being able to predict the gene bearing the disease-causing mutation will significantly reduce the time and cost of genetic sequencing.
Identifying the specific gene underlying a heritable arrhythmic disorder is of pivotal importance as increasingly developing genotype/phenotype correlations help individualized risk identification and patient management.
|
4 years
|
correlation of treatments with Cx43 distribution
Time Frame: 4 years
|
Another potential outcome has to do with the effect changes in the patients' treatment plans may have on Cx43 distribution.
Cx43 is the major gap junction protein responsible for the electrical coupling of the cells.
It has been shown that patients with arrhythmic disorders show decreased distribution of Cx43 at the cell borders in their hearts and this has been associated with an increased risk for arrhythmias.
The investigators' preliminary studies show that patients with cardiomyopathies show Cx43 remodeling in their buccal mucosa.
If a patient seen at the arrhythmia service of St. George's shows Cx43 remodeling during initial sampling and in a follow-up visit his clinical care team deems necessary to change his treatment plan the investigators would like to study Cx43 distribution again during one of his/hers follow up visits.
If the new treatment plan results in restoration of Cx43, this finding may be an indication of successful arrhythmia management.
|
4 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Arrhythmias, Cardiac
- Cardiac Conduction System Disease
- Cardiomyopathies
- Heart Defects, Congenital
- Cardiovascular Abnormalities
- Brugada Syndrome
- Arrhythmogenic Right Ventricular Dysplasia
- Channelopathies
Other Study ID Numbers
- 16.0099
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Brugada Syndrome
-
Istituto di Fisiologia Clinica CNRAzienda Ospedaliero, Universitaria Pisana; Azienda USL Toscana Nord Ovest; Azienda... and other collaboratorsNot yet recruitingBrugada Syndrome 1Italy
-
Hospices Civils de LyonUnknownBrugada Syndrome Type 1France
-
Angelo AuricchioTerminatedBrugada Syndrome 1SBelgium, Italy, Switzerland
-
Universitair Ziekenhuis BrusselNot yet recruitingNo Specific Condition (Patients Without Brugada Syndrome)Belgium
-
Assiut UniversityNot yet recruitingBrugada ECG Patterns
-
IRCCS Policlinico S. DonatoRecruitingECG Brugada PatternItaly
-
Pacific Rim Electrophysiology Research InstituteUniversity of BordeauxRecruitingEarly Repolarization Syndrome | Brugada SyndromeThailand
-
Universitair Ziekenhuis BrusselRecruiting
-
Pacific Rim Electrophysiology Research InstituteAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)RecruitingBrugada SyndromeThailand, Netherlands
-
Abbott Medical DevicesCompleted
Clinical Trials on obtaining a buccal smear sample
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI); Montefiore Medical Center; American Cancer Society...Completed
-
Massachusetts General HospitalJohns Hopkins University; M.D. Anderson Cancer Center; National Cancer Institute... and other collaboratorsRecruitingOvarian Neoplasms | Fallopian Tube Neoplasms | Stage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Anna VlasovaRussian Medical Academy of Continuous Professional Education; Morozov Children...CompletedDrug TherapyRussian Federation
-
Centre Hospitalier Universitaire de NiceCompleted
-
Istanbul Training and Research HospitalBezmialem Vakif UniversityUnknown
-
Northwestern UniversityIcahn School of Medicine at Mount Sinai; National Psoriasis FoundationCompleted
-
Mayo ClinicRecruitingHematologic Neoplasms | Myeloid Malignancy | Cytopenia | Bone Marrow Failure Syndrome | Clonal Cytopenia of Undetermined Significance | Clonal Hematopoiesis of Indeterminate Potential | Low Risk Myelodysplastic Syndrome | Inherited Bone Marrow Failure Syndrome | Clonal Expansion | Hereditary Neoplastic... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingEndometrial Clear Cell Adenocarcinoma | Endometrial Dedifferentiated Carcinoma | Endometrial Serous Adenocarcinoma | Malignant Uterine Neoplasm | Endometrial Mucinous Adenocarcinoma | Uterine Corpus CarcinosarcomaUnited States
-
University Hospitals Coventry and Warwickshire...Abbott; Copan Italia SPA , Via F. Perotti, 10, 25125 Brescia, ItalyWithdrawnCervix DiseasesUnited Kingdom
-
Turku University HospitalOulu University HospitalRecruiting