Ignite Creation Date:
2025-12-24 @ 5:24 PM
Ignite Modification Date:
2026-02-19 @ 5:02 PM
Study NCT ID:
NCT03038750
Status:
TERMINATED
Last Update Posted:
2024-02-02
First Post:
2017-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Molecular Investigation of Genetic Factors in CArDiovascular Diseases Using an BIOresource of Healthy Volunteers
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D065626', 'term': 'Non-alcoholic Fatty Liver Disease'}, {'id': 'D003327', 'term': 'Coronary Disease'}, {'id': 'D006973', 'term': 'Hypertension'}, {'id': 'D020246', 'term': 'Venous Thrombosis'}, {'id': 'D054556', 'term': 'Venous Thromboembolism'}, {'id': 'D003324', 'term': 'Coronary Artery Disease'}], 'ancestors': [{'id': 'D005234', 'term': 'Fatty Liver'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D013927', 'term': 'Thrombosis'}, {'id': 'D016769', 'term': 'Embolism and Thrombosis'}, {'id': 'D013923', 'term': 'Thromboembolism'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D004608', 'term': 'Eligibility Determination'}, {'id': 'D055991', 'term': 'Health Records, Personal'}, {'id': 'D003710', 'term': 'Demography'}, {'id': 'D014894', 'term': 'Weights and Measures'}, {'id': 'D001794', 'term': 'Blood Pressure'}, {'id': 'D006339', 'term': 'Heart Rate'}, {'id': 'D044022', 'term': 'Receptor, Endothelin A'}, {'id': 'C436316', 'term': 'adiponutrin'}, {'id': 'D000074283', 'term': 'Endothelial Protein C Receptor'}, {'id': 'D000085542', 'term': 'Functional Status'}, {'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D009934', 'term': 'Organization and Administration'}, {'id': 'D006298', 'term': 'Health Services Administration'}, {'id': 'D008499', 'term': 'Medical Records'}, {'id': 'D011996', 'term': 'Records'}, {'id': 'D003625', 'term': 'Data Collection'}, {'id': 'D004812', 'term': 'Epidemiologic Methods'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D011154', 'term': 'Population Characteristics'}, {'id': 'D015991', 'term': 'Epidemiologic Measurements'}, {'id': 'D011634', 'term': 'Public Health'}, {'id': 'D004778', 'term': 'Environment and Public Health'}, {'id': 'D055986', 'term': 'Vital Signs'}, {'id': 'D010808', 'term': 'Physical Examination'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D006439', 'term': 'Hemodynamics'}, {'id': 'D002320', 'term': 'Cardiovascular Physiological Phenomena'}, {'id': 'D002943', 'term': 'Circulatory and Respiratory Physiological Phenomena'}, {'id': 'D017466', 'term': 'Receptors, Endothelin'}, {'id': 'D043562', 'term': 'Receptors, G-Protein-Coupled'}, {'id': 'D011956', 'term': 'Receptors, Cell Surface'}, {'id': 'D008565', 'term': 'Membrane Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D018000', 'term': 'Receptors, Peptide'}, {'id': 'D008562', 'term': 'Membrane Glycoproteins'}, {'id': 'D006023', 'term': 'Glycoproteins'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D000203', 'term': 'Activities of Daily Living'}, {'id': 'D012046', 'term': 'Rehabilitation'}, {'id': 'D006296', 'term': 'Health Services'}, {'id': 'D005159', 'term': 'Health Care Facilities Workforce and Services'}, {'id': 'D006304', 'term': 'Health Status'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 74}, 'patientRegistry': False}, 'statusModule': {'whyStopped': 'The delay due to suspending the study due to covid, subsequent problems in synthesis, supply and yield of BQ123, prevented completion of the study as planned.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2017-08-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2023-06-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-02-01', 'studyFirstSubmitDate': '2017-01-25', 'studyFirstSubmitQcDate': '2017-01-29', 'lastUpdatePostDateStruct': {'date': '2024-02-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-02-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2023-06-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Forearm Blood Flow (Arterial contractility)', 'timeFrame': '2 years', 'description': 'Arm 1 specific measurement to be measured using venous occlusion plethysmography. Outcome measure will compare results between case vs control groups.'}, {'measure': 'Blood Biochemistry (Lipoprotein composition/dynamics)', 'timeFrame': '2 years', 'description': 'Arm 2 specific measurement collectively comparing the lipid dynamic results between case vs control groups.'}, {'measure': 'EPCR levels/shedding', 'timeFrame': '2 years', 'description': 'Arm 3 specific measurement comparing results between case vs control groups.'}, {'measure': 'Platelet aggregation/function', 'timeFrame': '2 years', 'description': 'Arm 3 specific measurement to be measured by platelet coagulation function assay comparing results between case vs control groups.'}, {'measure': 'Endothelial permeability', 'timeFrame': '2 years', 'description': 'Arm 3 specific measurement to be measured by an endothelial permeability assay comparing results between case vs control groups.'}, {'measure': 'Leukocyte-endothelium adhesion', 'timeFrame': '2 years', 'description': 'Arm 3 specific measurement to be measured by a leukocyte-endothelium adhesion assay comparing results between case vs control groups.'}], 'secondaryOutcomes': [{'measure': 'Blood pressure', 'timeFrame': '2 years', 'description': 'All study arms comparing results between case vs control groups.'}, {'measure': 'Heart rate', 'timeFrame': '2 years', 'description': 'All study arms comparing results between case vs control groups.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Healthy Volunteers', 'Genetic Risk Markers for Cardiovascular Disease', 'Non-Alcoholic Fatty Liver Disease', 'Coronary Disease', 'Hypertension', 'Venous Thromboses', 'Venous Thromboembolism', 'Coronary Heart Disease', 'Coronary Artery Disease'], 'conditions': ['Cardiovascular Diseases']}, 'descriptionModule': {'briefSummary': "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).\n\nMembers 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.\n\nVolunteers 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.\n\nThe 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.\n\nFor 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.\n\nFor 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.\n\nThis study is funded from the BHF Cambridge Center of Excellence and the Wellcome Trust Institutional Strategic Support Fund."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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).', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Volunteers are homozygous for:\n\n * 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\n * 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\n * 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\n* Volunteers are aged between 18-50 years old\n* Volunteers have a BMI:\n\n * Arm 1: Between18.5-29.9\n * Arm 2: Between 25.0-39.9\n * Arm 3: Between 18.5-29.9\n* 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:\n\n * Arm 1: At least 4 hours\n * Arm 2: At least 8 hours (for visit 2 only)\n * Arm 3: At least 4 hours\n* Have given written informed consent to participate\n\nExclusion Criteria:\n\n* Volunteers with chronic diseases, including cardiovascular diseases, liver diseases, type 1 and type 2 diabetes autoimmune diseases and cancer\n* Biological first-degree relatives (parents, brothers, sisters or children) who are or have suffered from one of the conditions described above\n* Current smokers. Ex-smokers are suitable if they stopped smoking \\>10 years ago\n* Volunteers with a diagnosis of hypertension, or history of consistently high blood pressure readings, \\>140/90 mmHg\n* Volunteers with a diagnosis of hypercholesterolemia, or history of consistently high cholesterol levels, e.g. total cholesterol level \\>6 mmol/l\n* Volunteers have ≥3 alcoholic drinks per day"}, 'identificationModule': {'nctId': 'NCT03038750', 'acronym': 'CADBIO', 'briefTitle': 'Molecular Investigation of Genetic Factors in CArDiovascular Diseases Using an BIOresource of Healthy Volunteers', 'organization': {'class': 'OTHER', 'fullName': 'Cambridge University Hospitals NHS Foundation Trust'}, 'officialTitle': 'Molecular Investigation of Genetic Factors in CArDiovascular Diseases Using an BIOresource of Healthy Volunteers', 'orgStudyIdInfo': {'id': 'CADBIO'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'EDNRA Sub-study', 'description': "Study population will be split into two groups defined by the allele of EDNRA the participant possesses:\n\nParticipants Homozygous for the A-allele of EDNRA, are assigned to the 'case' group.\n\nParticipants that are Homozygous for the G-allele will be assigned to the 'control' group.\n\n20 participants will be recruited to each group, 40 in total.", 'interventionNames': ['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)']}, {'label': 'PNPLA3 Sub-study', 'description': "Study population will be split into two groups defined by the allele of PNPLA3 the participant possesses:\n\nParticipants Homozygous for the G-allele of PNPLA3, are assigned to the 'case' group.\n\nParticipants that are Homozygous for the C-allele of PNPLA3 will be assigned to the 'control' group.\n\n60 participants will be recruited to each group, 120 in total.", 'interventionNames': ['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)']}, {'label': 'PROCR Sub-study', 'description': "Study population will be split into two groups defined by the allele of PROCR the participant possesses:\n\nParticipants Homozygous for the G-allele of PROCR, are assigned to the 'case' group.\n\nParticipants that are Homozygous for the A-allele of PROCR will be assigned to the 'control' group.\n\n30 participants will be recruited to each group, 60 in total.", 'interventionNames': ['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)']}], 'interventions': [{'name': 'Eligibility and lifestyle restrictions check.', 'type': 'OTHER', 'description': 'Eligibility will be assessed at each study visit and participants will be informed in advance of their visit.', 'armGroupLabels': ['EDNRA Sub-study', 'PNPLA3 Sub-study', 'PROCR Sub-study']}, {'name': 'Medical history, demographic and lifestyle factors', 'type': 'OTHER', 'description': 'Medical History, participants demographics and lifestyle factors will be assessed by the participant completion of the medical history and ethnicity questionnaires.', 'armGroupLabels': ['EDNRA Sub-study', 'PNPLA3 Sub-study', 'PROCR Sub-study']}, {'name': 'Anthropometric measurements: height, weight, and body fat', 'type': 'OTHER', 'description': 'Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.', 'armGroupLabels': ['EDNRA Sub-study', 'PNPLA3 Sub-study', 'PROCR Sub-study']}, {'name': 'Blood pressure and heart rate', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['EDNRA Sub-study', 'PNPLA3 Sub-study', 'PROCR Sub-study']}, {'name': 'Forearm blood flow: Visit 1 (EDNRA)', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['EDNRA Sub-study']}, {'name': 'Forearm blood flow: Visit 2 (EDNRA)', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['EDNRA Sub-study']}, {'name': 'Blood biochemistry (PNPLA3)', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Blood EPCR function (PROCR)', 'type': 'OTHER', 'description': 'Blood sample taken will be analysed via ELISA and FACS.', 'armGroupLabels': ['PROCR Sub-study']}, {'name': 'Blood platelet coagulation and function (PROCR)', 'type': 'OTHER', 'description': 'Blood sample taken will be analysed using a Platelet coagulation and function assay.', 'armGroupLabels': ['PROCR Sub-study']}, {'name': 'Blood endothelial permeability (PROCR)', 'type': 'OTHER', 'description': 'Blood sample will be analysed in vitro using a permeability assay kit.', 'armGroupLabels': ['PROCR Sub-study']}, {'name': 'Blood leukocyte-endothelium adhesion (PROCR)', 'type': 'OTHER', 'description': 'Blood sample will be analysed in vitro using a leukocyte-endothelium adhesion assay.', 'armGroupLabels': ['PROCR Sub-study']}, {'name': 'Baseline Venepuncture (PNPLA3, Visit 1)', 'type': 'OTHER', 'description': 'Up to 25ml Blood will be taken.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Deuterium water - Loading dose 1 (PNPLA3, Visit 1)', 'type': 'OTHER', 'description': 'Loading dose of 3 g/kg body water.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Deuterium water - Loading dose 2 (PNPLA3, Visit 1)', 'type': 'OTHER', 'description': 'Loading dose of 3 g/kg body water.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Energy-balanced dinner (PNPLA3, Visit 1)', 'type': 'OTHER', 'description': 'Provided following baseline bloods and loading dose 1.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Fasting venepuncture (PNPLA3, Visit 2)', 'type': 'OTHER', 'description': 'Up to 25ml Blood will be taken.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Deuterium water - Maintenance dose (PNPLA3, Visit 2)', 'type': 'OTHER', 'description': 'every hour, maintenance dose 0.04 g/kg body water', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Consumption of high carbohydrate meal (PNPLA3, Visit 2)', 'type': 'OTHER', 'description': 'Provided following fasting blood sample.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Postprandial Venepuncture (PNPLA3, Visit 2)', 'type': 'OTHER', 'description': 'Up to 25ml Blood will be taken.', 'armGroupLabels': ['PNPLA3 Sub-study']}, {'name': 'Venepuncture (PROCR)', 'type': 'OTHER', 'description': 'Up to 50ml Blood will be taken.', 'armGroupLabels': ['PROCR Sub-study']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'CB1 8RN', 'city': 'Cambridge', 'country': 'United Kingdom', 'facility': 'Department of Public Health and Primary Care', 'geoPoint': {'lat': 52.2, 'lon': 0.11667}}], 'overallOfficials': [{'name': 'Dirk Paul, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Cambridge'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': '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.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Cambridge University Hospitals NHS Foundation Trust', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Cambridge', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Dirk Paul', 'investigatorAffiliation': 'Cambridge University Hospitals NHS Foundation Trust'}}}}