- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03038750
Molecular Investigation of Genetic Factors in CArDiovascular Diseases Using an BIOresource of Healthy Volunteers (CADBIO)
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.
Study Overview
Status
Conditions
Intervention / Treatment
- 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)
- 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)
- 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)
Study Type
Enrollment (Actual)
Contacts and Locations
Study Contact
- Name: Dirk Paul, PhD
- Phone Number: 01223 761918
- Email: dsp35@medschl.cam.ac.uk
Study Locations
-
-
-
Cambridge, United Kingdom, CB1 8RN
- Department of Public Health and Primary Care
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
Volunteers are homozygous for:
- Arm 1: The A-allele of rs6841581, they are assigned to the 'case' group. If they are homozygous for the G-allele, they are assigned to the 'control' group
- Arm 2: The G-allele of rs738409, they are assigned to the 'case' group. If they are homozygous for the C-allele, they are assigned to the 'control' group
- Arm 3: The G-allele of rs867186, they are assigned to the 'case' group. If they are homozygous for the A-allele, they are assigned to the 'control' group
- Volunteers are aged between 18-50 years old
Volunteers have a BMI:
- Arm 1: Between18.5-29.9
- Arm 2: Between 25.0-39.9
- Arm 3: Between 18.5-29.9
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:
- Arm 1: At least 4 hours
- Arm 2: At least 8 hours (for visit 2 only)
- Arm 3: At least 4 hours
- Have given written informed consent to participate
Exclusion Criteria:
- Volunteers with chronic diseases, including cardiovascular diseases, liver diseases, type 1 and type 2 diabetes autoimmune diseases and cancer
- Biological first-degree relatives (parents, brothers, sisters or children) who are or have suffered from one of the conditions described above
- Current smokers. Ex-smokers are suitable if they stopped smoking >10 years ago
- Volunteers with a diagnosis of hypertension, or history of consistently high blood pressure readings, >140/90 mmHg
- Volunteers with a diagnosis of hypercholesterolemia, or history of consistently high cholesterol levels, e.g. total cholesterol level >6 mmol/l
- Volunteers have ≥3 alcoholic drinks per day
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
EDNRA Sub-study
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. |
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.
|
PNPLA3 Sub-study
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. |
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.
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.
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.
|
PROCR Sub-study
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. |
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.
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 50ml Blood will be taken.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Forearm Blood Flow (Arterial contractility)
Time Frame: 2 years
|
Arm 1 specific measurement to be measured using venous occlusion plethysmography.
Outcome measure will compare results between case vs control groups.
|
2 years
|
Blood Biochemistry (Lipoprotein composition/dynamics)
Time Frame: 2 years
|
Arm 2 specific measurement collectively comparing the lipid dynamic results between case vs control groups.
|
2 years
|
EPCR levels/shedding
Time Frame: 2 years
|
Arm 3 specific measurement comparing results between case vs control groups.
|
2 years
|
Platelet aggregation/function
Time Frame: 2 years
|
Arm 3 specific measurement to be measured by platelet coagulation function assay comparing results between case vs control groups.
|
2 years
|
Endothelial permeability
Time Frame: 2 years
|
Arm 3 specific measurement to be measured by an endothelial permeability assay comparing results between case vs control groups.
|
2 years
|
Leukocyte-endothelium adhesion
Time Frame: 2 years
|
Arm 3 specific measurement to be measured by a leukocyte-endothelium adhesion assay comparing results between case vs control groups.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood pressure
Time Frame: 2 years
|
All study arms comparing results between case vs control groups.
|
2 years
|
Heart rate
Time Frame: 2 years
|
All study arms comparing results between case vs control groups.
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dirk Paul, PhD, University of Cambridge
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CADBIO
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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 Cardiovascular Diseases
-
Medical College of WisconsinRecruitingCardiovascular Diseases | Cardiovascular Risk Factor | Cardiovascular HealthUnited States
-
Hospital Mutua de TerrassaCompleted
-
Oregon Health and Science UniversityCompletedCardiovascular Disease | Cardiovascular Risk FactorsUnited States
-
Women's College HospitalUniversity Health Network, Toronto; Sunnybrook Health Sciences Centre; Brigham... and other collaboratorsUnknownCARDIOVASCULAR DISEASESCanada, United States
-
Groupe Hospitalier Paris Saint JosephTerminatedCARDIOVASCULAR DISEASESFrance
-
University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
-
VA Office of Research and DevelopmentNot yet recruitingCardiovascular DiseaseUnited States
-
Baptist Health South FloridaUniversity of California, Los Angeles; Quest Diagnostics-Nichols InsituteActive, not recruitingCardiovascular DiseaseUnited States
-
Laval UniversityActive, not recruitingCardiovascular DiseaseCanada
-
Penn State UniversityCalifornia Healthcare InstituteCompleted
Clinical Trials on Eligibility and lifestyle restrictions check.
-
Bibi GramCompletedMusculoskeletal DiseasesDenmark
-
University of PennsylvaniaGilead SciencesCompletedHepatitis C | Hepatitis C, ChronicUnited States
-
Wayne State UniversityCompleted
-
Brown UniversityCompletedSubstance Use | Risky Sexual BehaviorUnited States
-
CloSys CorporationEminence Clinical Research, Inc.TerminatedSealing the ArteriotomyUnited States
-
Boston UniversityBill and Melinda Gates Foundation; University of Witwatersrand, South AfricaCompletedHIV/AIDS | Antiretroviral TherapySouth Africa
-
4th Military Clinical Hospital with Polyclinic,...Recruiting
-
Denise WalkerNational Institute on Drug Abuse (NIDA); Virginia Polytechnic Institute and...CompletedCannabis Use Disorder
-
Brown UniversityJohns Hopkins University; Meals on Wheels AmericaRecruiting
-
University of PittsburghNational Heart, Lung, and Blood Institute (NHLBI)RecruitingDiabetes | Overweight | Hypertension, Pregnancy-Induced | Hypertension in Pregnancy | Obesity, MaternalUnited States