Cardiovascular Longitudinal ALSPAC Research Investigations Following Hypertensive Pregnancy in Young Adulthood

Hypertension Clinical Trial

— CLARITY  

Official title:

Cardiovascular Longitudinal the Avon Longitudinal Study of Parents and Children (ALSPAC) Research Investigations Following Hypertensive Pregnancy in Young Adulthood

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683093
• Other study ID #: 22/WA/0227
• Status: Recruiting
• Start date: November 17, 2022
• Est. completion date: January 31, 2027

Study information

• Verified date: January 2023
• Source: University of Oxford
• Contact: Katie Suriano
• Phone: 01865 226845
• Email: clarity[@]cardiov.ox.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to understand more about why young people who were born to a hypertensive pregnancy may have increased risk of high blood pressure and are often at increased risk of heart and blood vessel disease later in life.

Description:

Women who develop blood pressure problems during pregnancy are more likely to have high blood pressure (hypertension) in later life as well as heart attacks or strokes. The children born to the pregnancy also tend to have higher blood pressure and are often at increased risk of heart and blood vessel disease later in life. Previous work has shown that children born to pregnancies where the mother has high blood pressure have changes in their blood vessels, heart and brain that can be measured long before they develop high blood pressure or other clinical symptoms. By understanding the pattern of changes cross multiple parts of the body, over a lifetime, the investigators can identify how advanced the underlying disease is for an individual and how their disease is likely to develop over the next few years.

The aim of this study is to understand the heart and blood vessel changes of people born to a hypertensive pregnancy once they are in their 20s and 30s. The investigators then hope to use this information to develop new ways to prevent early onset heart and blood vessel disease in these people.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2027
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 40 Years

Eligibility

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study

• Male or female, aged 30 to 40 years at time of enrolment

• Participant previously took part in the ALSPAC study

• Able (in the investigator's opinion) and willing to comply with all study requirements

• Adequate understanding of verbal and written English

Exclusion Criteria:

• Pregnant or lactating when they are due to attend for study visit 1

• Less than six months postpartum

• Planning to donate blood within two weeks prior to study visit 1

• Any significant disease or disorder which, in the opinion of the investigator, might influence the participant's ability to participate in the study

• Evidence of congenital heart disease or significant chronic disease relevant to cardiovascular or metabolic status

For exclusion of MRI component only:

• Unsuitable for MRI based on participant screening; the participant may still be included in other parts of the study

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cerebrovascular Diseases
• Cerebrovascular Disorders
• Hypertension
• Hypertension in Pregnancy
• Hypertension, Pregnancy-Induced
• Vascular Diseases
• Young Adult

Intervention

Other:
• History of being born to hypertensive or normal pregnancy
CLARITY is an observational study whereby participants will attend one 4-hr visit the Division of Cardiovascular Medicine, University of Oxford at the John Radcliffe Hospital in Oxford, with the option to split the study visit over two days for convenience. Participants will be invited by the ALSPAC study team to attend a study visit in Oxford where the investigators will use MRI and other imaging modalities to study the brain, heart, liver, kidneys, and vasculature using standardised protocols. A dataset including information from previous follow-up of these cohorts and the detailed pregnancy data available within ALSPAC will be generated by the study team in Bristol and integrated with available data from the Oxford cohorts.

Locations

Country	Name	City	State
United Kingdom	University of Oxford	Oxford	Oxfordshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	University of Bristol

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac right ventricular mass	Magnetic resonance imaging (MRI) assessment of cardiac right ventricular mass indexed to body surface area (in g and g/m^2)	30-40 years of old
Secondary	Cardiac left ventricular mass	MRI assessment of cardiac left ventricular mass indexed to body surface area (in g and g/m^2)	30-40 years of old
Secondary	Cardiac right ventricular end-diastolic volume	MRI assessment of cardiac right ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Secondary	Cardiac right ventricular stroke volume	MRI assessment of cardiac right ventricular stroke volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Secondary	Cardiac left ventricular end-diastolic volume	MRI assessment of cardiac left ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Secondary	Cardiac left ventricular stroke volume	MRI assessment of cardiac left ventricular stroke volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Secondary	Cardiac right ventricular systolic function	Echocardiography and MRI assessment of right ventricular systolic function: tricuspid annular plane systolic excursion (in cm) and right ventricular ejection fraction measured by cardiac MRI (in %)	30-40 years of old
Secondary	Cardiac left ventricular systolic function	Echocardiography and MRI assessment of left ventricular systolic function: left ventricular ejection fraction (in %)	30-40 years of old
Secondary	Cardiac right ventricular diastolic function	Echocardiography assessment of right ventricular (RV) diastolic function: RV Doppler early/late diastolic tricuspid inflow velocity ratio (E/A)	30-40 years of old
Secondary	Cardiac left ventricular diastolic function	Echocardiography assessment of left ventricular (LV) diastolic function: LV Doppler early/late diastolic mitral inflow velocity ratio (E/A) and LV early Doppler inflow velocity/peak early diastolic tissue velocity ratio (E/e')	30-40 years of old
Secondary	Morphology of the right ventricles	MRI assessment of the right ventricles morphology using cardiac statistical atlas and principal component analysis	30-40 years of old
Secondary	Morphology of the left ventricles	MRI assessment of the left ventricles morphology using cardiac statistical atlas and principal component analysis	30-40 years of old
Secondary	Aortic compliance	Aortic distensibility by MRI (in 10^-3 mmHg^-1) and aortic/central blood pressure by cuff measurement (in mmHg)	30-40 years of old
Secondary	Intra-hepatic lipid content, steatohepatitis and hepatic fibrosis	MRI assessment of the liver to quantify proton density fat fraction (in %) and fibro-inflammatory status from iron-corrected T1 (cT1 in ms)	30-40 years of old
Secondary	Renal function	MRI assessment of fibro-inflammatory status from T1 (in ms) and surrogate measure of blood perfusion from T2* (in ms) and volumes (in ml and ml/m^2)	30-40 years of old
Secondary	Oxygen uptake across sub-maximal and peak exercise	Cardiopulmonary exercise test to measure oxygen uptake (VO2 in ml/kg/min)	30-40 years of old
Secondary	Carbon dioxide exchange kinetics across sub-maximal and peak exercise	Cardiopulmonary exercise test to measure respiratory exchange ratio (RER calculated as carbon dioxide production divided by oxygen consumption)	30-40 years of old
Secondary	Retinal arteriolar structure	Central retinal arteriolar equivalent (CRAE in µm) measured using retinal imaging	30-40 years of old
Secondary	Retinal venular structure	Central retinal venular equivalent (CRVE in µm) measured using retinal imaging	30-40 years of old
Secondary	Retinal arteriolar-to-venular diameter ratio (AVR)	The ratio of average retinal arteriolar diameter (CRAE in µm) and average retinal venous diameter (CRVE in µm) measured using retinal imaging	30-40 years of old
Secondary	Ear microvascular structure	Superior crus of anti-helix earlobe vascular caliber (in µm) measured using ear vascular imaging	30-40 years of old
Secondary	Lung function	The forced expiratory volume in one second (FEV1 in L), forced vital capacity (FVC in L), and the ratio of FEV1 to FVC (FEV1/FVC) measured using spirometry	30-40 years of old
Secondary	Objective measure of physical activity	The amount of moderate to vigorous physical activity (in h/week) and vigorous physical activity (in h/week) measured using wrist worn accelerometer	30-40 years of old
Secondary	Total white matter volume	Total white matter volumes (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Secondary	Total grey matter volume	Total grey matter volumes (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Secondary	Subcortical brain volume of thalamus	Subcortical brain volume of thalamus (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Secondary	Subcortical brain volume of hippocampus	Subcortical brain volume of hippocampus (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Secondary	White matter hyperintensities volume	Total volume of white matter hyperintensities (in mm3) assessed on T2-weighted sequence of brain MRI	30-40 years of old
Secondary	White matter hyperintensities count	The number of white matter hyperintensities on T2-weighted sequence of brain MRI	30-40 years of old
Secondary	Cerebral vessel lumen diameter	Cerebral vessel lumen diameter (in µm) assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Secondary	Cerebral vessel density	Cerebral vessel density (in mm3) assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Secondary	Cerebral vessel tortuosity	The ratio of cerebral vessel tortuosity assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Secondary	Whole brain grey matter perfusion or cerebral blood flow (CBF)	Whole brain grey matter perfusion/CBF (in ml/100g/min) assessed on arterial spin labelling of brain MRI	30-40 years of old
Secondary	Arterial cerebral blood volume fraction	Arterial cerebral blood volume fraction (in %) assessed on arterial spin labelling of brain MRI	30-40 years of old
Secondary	Circulating vascular endothelial growth factor A (VEGF-A) as an angiogenic marker	The level of VEGF-A (in pg/mL) measured from plasma blood samples	30-40 years of old
Secondary	Circulating soluble endoglin (sENG) as an angiogenic marker	The level of sENG (in ng/mL) measured from plasma blood samples	30-40 years of old
Secondary	Circulating soluble fms-like tyrosine kinase-1 (sFlt-1) as an antiangiogenic marker	The level of sFlt-1 (in pg/mL) measured from plasma blood samples	30-40 years of old
Secondary	Circulating total cholesterol as a metabolic marker	The level of total cholesterol (in mmol/L) measured from serum blood samples	30-40 years of old
Secondary	Circulating high-density lipoprotein as a metabolic marker	The level of HDL (in mmol/L) measured from serum blood samples	30-40 years of old
Secondary	Circulating low-density lipoprotein as a metabolic marker	The level of LDL (in mmol/L) measured from serum blood samples	30-40 years of old
Secondary	Circulating triglycerides as a metabolic marker	The level of triglycerides (in mmol/L) measured from serum blood samples	30-40 years of old
Secondary	Circulating fasting glucose concentration as a metabolic marker	The level of fasting glucose (in mmol/L) measured from whole blood samples	30-40 years of old
Secondary	Circulating fasting insulin concentration as a metabolic marker	The level of fasting insulin (in pmol/L) measured from serum blood samples	30-40 years of old
Secondary	Insulin resistance index (HOMA-IR) as a metabolic marker	The index calculated as fasting glucose (in mmol/L) x fasting insulin (in µIU/mL) ÷ 22.5	30-40 years of old
Secondary	Circulating C-reactive protein (CRP) as an inflammatory marker	The level of CRP (in mmol/L) measured from serum blood samples	30-40 years of old
Secondary	Circulating soluble intercellular adhesion molecule-1 (sICAM-1) as an inflammatory marker	The level of sICAM-1 (in ng/mL) measured from serum blood samples	30-40 years of old
Secondary	Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) as an inflammatory marker	The level of sVCAM-1 (in ng/mL) measured from serum blood samples	30-40 years of old
Secondary	Body weight	Body weight measured in kg	30-40 years of old
Secondary	Body height	Body height measured in m	30-40 years of old
Secondary	Body mass index	Body weight divided by the square of height (in kg/m2)	30-40 years of old
Secondary	Mid-arm circumference	Mid-arm circumference measured in cm	30-40 years of old
Secondary	Waist-to-hip ratio	The ratio of waist circumference (in cm) to hip circumference (in cm)	30-40 years of old
Secondary	Systolic blood pressure	Resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Secondary	Diastolic blood pressure	Resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Secondary	Mean arterial pressure	The average arterial pressure from resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Secondary	Pulse pressure	The difference between systolic and diastolic blood pressure (in mmHg)	30-40 years of old
Secondary	Heart rate	The frequency of the heart contractions per minute (in beats per minute or bpm)	30-40 years of old
Secondary	Smoking status	The number and percentage of current smokers	30-40 years of old
Secondary	Alcohol consumption	Weekly alcoholic unit intake (in units per week)	30-40 years of old