Targeting Microvascular Dysfunction in Young Hypertensive Patients

Cholesterol and blood pressure lowering tablets have been shown to be of benefit in patients with established high blood pressure. High blood pressure is a very common medical condition that can lead to vascular complications i.e. problems with the blood vessels in the body. One way of detecting early changes in these blood vessels as a result of high blood pressure is to measure their compliance/flexibility with a noninvasive technique known as ultrasound and with a simple blood test. The investigators are trying to establish whether these early changes in blood vessels can be significantly improved by the use of both a cholesterol and blood pressure lowering tablet at an earlier stage than is currently advised. The investigators hope that the early combination of these tablets will prove more effective than the use of a blood pressure lowering tablet by itself and therefore possibly reduce the risk of long term complications developing.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension
• Intervention / Treatment: Drug: Simvastatin; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7BL
    • Belfast Health and Social Care Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• To be eligible for the study, all of the following criteria must be met:

  • All patients must have a diagnosis of essential hypertension with off treatment systolic pressure >140 mmHg and/or diastolic pressure >90 mmHg, measured at rest in the seated position on at least two separate occasions, at least 2 weeks apart.
  • Patients will be < 50 years for men and < 60 years for women.
  • Female patients of childbearing potential must be using a medically accepted means of contraception (that is, interuterine device, oral contraceptive, implant, DepoProvera or barrier devices). Female patients of childbearing age will be screened with a pregnancy test.
  • Patients will be typically already on antihypertensive therapy.
  • Patients must have a level of understanding sufficient to complete all tests and examinations required by the protocol and are able to understand and give informed consent.

Exclusion Criteria:

• Patients will be excluded from the study if they meet any of the following criteria:

  • A history of diabetes mellitus, coronary artery or cerebrovascular disease, hypertensive retinopathy, hypertensive nephropathy, left ventricular hypertrophy or hyperlipidaemia warranting treatment as defined by the latest NICE guidelines which recommend an age based treatment strategy rather than one driven purely by lipid levels in isolation.
  • Abnormal baseline liver function (defined as AST or ALT > 3 times upper limit of normal), raised baseline creatinine kinase (CK) (defined as CK > 200 mmol/L), severe renal impairment (defined as estimated glomerular filtration rate (eGFR) < 30 mls/minute) or previous adverse event relating to either an ARB or statin in the past.
  • Female patients will be excluded if they are pregnant, intend to be pregnant or are lactating. Female patients of childbearing age will be screened with a pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin; 40mg Simvastatin once daily for 12 weeks followed by 4 week washout period followed by placebo for 12 weeks	Drug: Simvastatin; 40mg encapsulated once daily for 12 weeks
Placebo Comparator: Placebo; Placebo for 12 weeks followed by 4 week washout period followed by 40mg Simvastatin once daily for 12 weeks	Drug: Placebo; Encapsulated oral once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To demonstrate a significant difference in flow-mediated dilatation of the brachial artery and microvasculature between groups.	0, 3, 4 and 7 months

Collaborators and Investigators

• Sponsor: Queen's University, Belfast
• Collaborators: Belfast Health and Social Care Trust
• Investigators: Principal Investigator: Gary E McVeigh, FRCP PhD, Queen's University, Belfast

Publications and helpful links

General Publications

• Bleakley C, McCann A, McClenaghan V, Hamilton PK, Millar A, Pumb R, Harbinson M, McVeigh GE. Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients. Cardiovasc Ultrasound. 2015 Mar 20;13:12. doi: 10.1186/s12947-015-0006-7.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): August 1, 2011

Study Registration Dates

• First Submitted: January 11, 2010
• First Submitted That Met QC Criteria: January 11, 2010
• First Posted (Estimate): January 12, 2010

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Hypertension endothelial dysfunction statin prevention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 2009-011638-90