An observational study in Cardiovascular Diseases, sponsored by Cambridge University Hospitals NHS Foundation Trust. Terminated at 1 site in United Kingdom. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-02.
Sponsored by Cambridge University Hospitals NHS Foundation Trust · Observational
The risk of cardiovascular disease is determined by the complex interplay between an individual's genetic make-up, lifestyle, and the environment. We are investigating three potential genetic risk factors in this observational, cross-sectional, epidemiology pilot study to investigate if and how functional variants identified in large-scale genome wide association studies can explain a predisposition to cardiovascular disease. By determining the molecular mechanisms that are regulated at the EDNRA, PNPLA3 and PROCR CVD risk loci, we hope to translate findings from this study into the clinical setting for better diagnosis, prevention and treatment for patients suffering with cardiovascular disease. Volunteers will enter into one of the study's three arms based on their genotype: EDNRA locus (Arm 1), PNPLA3 locus (Arm 2), or PROCR locus (Arm 3).
Members of the Cambridge Bioresource who match for the target alleles will be invited to participate and will enter into one of the three study arms. All study assessment visits will take place at Addenbrooke's Hospital in collaboration with the University of Cambridge.
Volunteers will participate in the study for a maximum of 12 months and depending on study arm they are assigned to, 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. Minimally invasive procedures including forearm blood flow and venepuncture will be performed to assess the primary objectives of the study.
The hypothesis for arm 1 is that the genetic variant we are investigating at the EDNRA gene locus alters the function of the endothelin receptor A leading to an increased risk of coronary artery disease and large artery stroke.
For study arm 2, we hypothesize that the genetic variant we are investigating in PNPLA3 will increase the risk of Non-alcoholic fatty liver disease but reduce the risk of Coronary Heart Disease.
For study arm 3, we hypothesize that the genetic variant we are investigating in the PROCR locus triggers molecular events that potentially increase the risk of Venous Thrombosis/Venous Thromboembolism nut reducing blood pressure. Furthermore we aim to investigate the anti-inflammatory effects to see if there is an effect on explaining reduced risk of CHD.
This study is funded from the BHF Cambridge Center of Excellence and the Wellcome Trust Institutional Strategic Support Fund.
4,902 studies on the registry are indexed under Cardiovascular Diseases; 920 are open to participants now.
This study's enrollment of 74 is below the median of 573 across 1,483 observational studies indexed under Cardiovascular Diseases.
Browse Cardiovascular Diseases studies →Cambridge University Hospitals NHS Foundation Trust is the lead sponsor of 167 studies on the registry; 37 are open to participants now.
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The study will only recruit healthy volunteers who have previously consented to being contacted for future studies by the NIHR Cambridge BioResource which is a panel of around 20,000 volunteers, both with and without health conditions, who are willing to be approached to participate in research studies investigating the links between genes, the environment, health and disease. Volunteers who join the Cambridge BioResource have donated their DNA via a blood or saliva sample which is used together with other information, such as gender and ethnicity, to match them to specific research studies. Participants for this study are therefore identified by having the appropriate genetic sequence in one of the three genetic loci we are investigating (EDNRA, PNPLA3 or PROCR).
Volunteers are homozygous for:
Volunteers have a BMI:
Volunteers are willing not to consume products containing alcohol or caffeine 12 hours prior to procedures. Additionally, volunteers must agree to fast before procedures for:
Exclusion Criteria:
Study population will be split into two groups defined by the allele of EDNRA the participant possesses: Participants Homozygous for the A-allele of EDNRA, are assigned to the 'case' group. Participants that are Homozygous for the G-allele will be assigned to the 'control' group. 20 participants will be recruited to each group, 40 in total.
Other: Eligibility and lifestyle restrictions check. · Other: Medical history, demographic and lifestyle factors · Other: Anthropometric measurements: height, weight, and body fat · Other: Blood pressure and heart rate · Other: Forearm blood flow: Visit 1 (EDNRA) · Other: Forearm blood flow: Visit 2 (EDNRA)
Study population will be split into two groups defined by the allele of PNPLA3 the participant possesses: Participants Homozygous for the G-allele of PNPLA3, are assigned to the 'case' group. Participants that are Homozygous for the C-allele of PNPLA3 will be assigned to the 'control' group. 60 participants will be recruited to each group, 120 in total.
Other: Eligibility and lifestyle restrictions check. · Other: Medical history, demographic and lifestyle factors · Other: Anthropometric measurements: height, weight, and body fat · Other: Blood pressure and heart rate · Other: Blood biochemistry (PNPLA3) · Other: Baseline Venepuncture (PNPLA3, Visit 1) · Other: Deuterium water - Loading dose 1 (PNPLA3, Visit 1) · Other: Deuterium water - Loading dose 2 (PNPLA3, Visit 1) · Other: Energy-balanced dinner (PNPLA3, Visit 1) · Other: Fasting venepuncture (PNPLA3, Visit 2) · Other: Deuterium water - Maintenance dose (PNPLA3, Visit 2) · Other: Consumption of high carbohydrate meal (PNPLA3, Visit 2) · Other: Postprandial Venepuncture (PNPLA3, Visit 2)
Study population will be split into two groups defined by the allele of PROCR the participant possesses: Participants Homozygous for the G-allele of PROCR, are assigned to the 'case' group. Participants that are Homozygous for the A-allele of PROCR will be assigned to the 'control' group. 30 participants will be recruited to each group, 60 in total.
Other: Eligibility and lifestyle restrictions check. · Other: Medical history, demographic and lifestyle factors · Other: Anthropometric measurements: height, weight, and body fat · Other: Blood pressure and heart rate · Other: Blood EPCR function (PROCR) · Other: Blood platelet coagulation and function (PROCR) · Other: Blood endothelial permeability (PROCR) · Other: Blood leukocyte-endothelium adhesion (PROCR) · Other: Venepuncture (PROCR)
Eligibility will be assessed at each study visit and participants will be informed in advance of their visit.
Medical History, participants demographics and lifestyle factors will be assessed by the participant completion of the medical history and ethnicity questionnaires.
Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.
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.
Intra-arterial infusion of Phenylephrine at doses of 0.75, 2.5, and 7.5 μg/min for 6 min each (18 min in total). FBF measured in the last 3 minutes. There will be a 30 minute washout with saline followed by Endothelin-1 infusion of at a dose of 5 pmol/min for 90 min.
Intra-arterial infusion of Sodium nitroprusside infusion at doses of 1, 3, and 10 μg/min for 6 min each (18 min in total). FBF measured in the last 3 minutes. There will be a 20 minute washout with saline followed by infusion of BQ-123 at a dose of 10 nmol/min for 90 min.
25ml blood will be taken from the participant in a glucose fasting state. Following a high carbohydrate meal, a second 25ml blood sample will be taken. Clinical Biochemistry tests and detailed lipid analysis will be performed.
Blood sample taken will be analysed via ELISA and FACS.
Blood sample taken will be analysed using a Platelet coagulation and function assay.
Blood sample will be analysed in vitro using a permeability assay kit.
Blood sample will be analysed in vitro using a leukocyte-endothelium adhesion assay.
Up to 25ml Blood will be taken.
Loading dose of 3 g/kg body water.
Loading dose of 3 g/kg body water.
Provided following baseline bloods and loading dose 1.
Up to 25ml Blood will be taken.
every hour, maintenance dose 0.04 g/kg body water
Provided following fasting blood sample.
Up to 25ml Blood will be taken.
Up to 50ml Blood will be taken.
Forearm Blood Flow (Arterial contractility)
Arm 1 specific measurement to be measured using venous occlusion plethysmography. Outcome measure will compare results between case vs control groups.
Time frame: 2 years
Blood Biochemistry (Lipoprotein composition/dynamics)
Arm 2 specific measurement collectively comparing the lipid dynamic results between case vs control groups.
Time frame: 2 years
EPCR levels/shedding
Arm 3 specific measurement comparing results between case vs control groups.
Time frame: 2 years
Platelet aggregation/function
Arm 3 specific measurement to be measured by platelet coagulation function assay comparing results between case vs control groups.
Time frame: 2 years
Endothelial permeability
Arm 3 specific measurement to be measured by an endothelial permeability assay comparing results between case vs control groups.
Time frame: 2 years
Leukocyte-endothelium adhesion
Arm 3 specific measurement to be measured by a leukocyte-endothelium adhesion assay comparing results between case vs control groups.
Time frame: 2 years
Blood pressure
All study arms comparing results between case vs control groups.
Time frame: 2 years
Heart rate
All study arms comparing results between case vs control groups.
Time frame: 2 years
Plan to share: No — Participant identifiable information is securely held, with restricted access, by the NIHR BioResource. Members of the research team carrying out the procedures will not be able to request the link to decode this information. Only the minimum required participant identifiable information (name and contact details) will be provided to the research team for the purpose of arranging study visits and completing the informed consent process. All research personnel will be sufficiently blinded of the genotype status of the healthy volunteers. All delegated research personnel that is responsible to conduct the data/statistical analysis will only analyse data that is anonymised of any patient identifiable data.
No publications or documents are linked to this record.
This study is terminated, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Cambridge University Hospitals NHS Foundation Trust