Molecular Investigation of GENetic Factors in Cardiovascular and Immune-related Traits and Diseases Using a BIOresource of Healthy Volunteers (GENBIO)

Cardiovascular Diseases Clinical Trial

— GENBIO  

Official title:

Molecular Investigation of GENetic Factors in Cardiovascular and Immune-related Traits and Diseases Using a BIOresource of Healthy Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04931498
• Other study ID #: GENBIO
• Status: Recruiting
• Start date: March 1, 2018
• Est. completion date: September 30, 2024

Study information

• Verified date: February 2024
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: Dirk Paul, PhD
• Phone: 01223 761918
• Email: dsp35[@]medschl.cam.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The risk of cardiovascular disease is determined by the complex interplay between an individual's genetic make-up, lifestyle, and the environment. The researchers in this observational, cross-sectional, recall-by-genotype study are investigating two potential genetic risk factors; the SWAP70 gene is thought to play a role in the immune response modulating cardiovascular disease risk and the GMPR gene plays a role in red blood cell formation. The investigators hope to identify and characterise distinct molecular and cellular mechanisms underlying candidate functional variants identified in genetic studies of cardiovascular and immune-related human traits and diseases.

Healthy volunteers who are part of the NIHR BioResource and have already been genotyped will be invited to the study based on their genotype of the candidate functional variants of interest. Volunteers will attend a single study visit, during which they will complete procedures including a medical, demographic and lifestyle factors questionnaire; height, weight and body fat assessments; in addition to blood pressure/heart rate measurements. A minimally invasive procedure of a venepuncture will be performed to assess the primary objectives of the study.

The obtained data may (1) improve understanding of biological and disease mechanisms; (2) identify potential drug targets; and (3) improve insight into the therapeutic potential and limitations of existing and emerging therapies.

This study is funded by the UK Medical Research Council, British Heart Foundation and NIHR Cambridge Biomedical Research Centre.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have consented to be part of the NIHR BioResource;

• Are aged 18 years and above;

• Have given written informed consent to participate in the GENBIO study;

• Are carriers or non-carriers of the candidate functional genetic variant(s) of interest.

Exclusion Criteria:

Have a chronic disease, including cardiovascular diseases, autoimmune diseases and cancer.

Additional exclusion criteria to be applied at the discretion/opinion of the CI/collaborator, based on the population of available volunteers for recall and the genetic variant of interest (e.g. allele frequency):

• Have a biological first-degree relatives (parents, brothers, sisters or children) who are suffering or have suffered from a disease/condition in the opinion of the CI/collaborator that, from a genetic standpoint, may affect the study validity;

• Are current regular smokers. Regular ex-smokers are suitable if they stopped smoking >10 years ago (regular defined as 1 pack year in both instances);

• Have =3 alcoholic drinks per day;

• Have a diagnosis of hypertension, or history of consistently high blood pressure readings, e.g. >140/90 mmHg;

• Have a diagnosis of hypercholesterolemia, or history of consistently high cholesterol levels, e.g. total cholesterol level >6 mmol/l;

• Are obese (i.e. BMI >30);

• Are unwilling to fast and not to consume products containing alcohol or caffeine 12 hours prior to procedures.

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Other:
• Questionnaire
Medical history, demographics and lifestyle factors will be assessed by the participant.
• Anthropometric measurements: height, weight, and body fat
Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.
• Blood pressure and heart rate
Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Procedure:
• Venepuncture (GMPR)
A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests: Flow cytometry to quantify cell surface expression of key erythroid markers Proteomic analysis of isolated erythrocytes using mass spectrometry
• Venepuncture (SWAP70)
A blood sample of approximately 50 ml of venous blood will be taken. From the obtained blood sample, measurements will include a full blood count and the following phenotyping tests: Flow cytometry to quantify cell surface expression of key markers Fluorescence-Activated Cell Sorting (FACS) to assess B-cell receptor signalling and to isolate cell type-specific RNA for transcriptome analysis Immunoglobulin isotype titre analysis in plasma Isolation of monocytes for subsequent use in phagocytosis assays

Locations

Country	Name	City	State
United Kingdom	Department of Public Health and Primary Care	Cambridge	Cambridgeshire

Sponsors (2)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust	University of Cambridge

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Levels of GMPR protein in isolated erythrocytes	GMPR-specific measurement to be assessed by mass spectrometry, comparing results between different GMPR genotypic groups.	At baseline
Primary	Levels of SWAP70 protein in immune cell subsets	SWAP70-specific measurement to be assessed by flow cytometry, comparing results between SWAP70 genotypic groups.	At baseline
Primary	Proportion of immune cell types as measured using flow cytometric analysis	SWAP70-specific measurement to be assessed by flow cytometry (e.g. lymphoid and myeloid cell markers), comparing results between SWAP70 genotypic groups.	At baseline
Primary	Levels of genes/transcripts in immune cell subsets	SWAP70-specific measurement to be assessed by RNA sequencing, comparing results between SWAP70 genotypic groups.	At baseline
Primary	Concentration of immunoglobulin isotypes in plasma	SWAP70-specific measurement to be assessed by immunoglobulin isotype (IgM, IgG, IgA and IgE) analysis, comparing results SWAP70 genotypic groups.	At baseline
Primary	Phagocytosis by monocytes as measured by colorimetric analysis (optical density)	SWAP70-specific measurement to be assessed by phagocytosis assays, comparing results between SWAP70 genotypic groups. The phagocytosis assay uses pre-labelled Zymosan particles as a pathogen for triggering phagocytosis. The engulfed Zymosan particles react with a specific substrate to produce a signal that can be detected by colorimetric analysis.	At baseline
Secondary	Blood pressure (systolic and diastolic)	All study arms comparing results between genotypic groups.	At baseline
Secondary	Heart rate	All study arms comparing results between genotypic groups.	At baseline