Intensive Blood Pressure Control in Ischaemic Stroke Patients With Severe Cerebral Small Vessel Disease

January 10, 2023 updated by: Dr. Gary Kui Kai LAU, The University of Hong Kong

Effect of Intensive Blood Pressure Control on Cerebral Blood Flow and Cognition in Ischaemic Stroke Patients With Severe Cerebral Small Vessel Disease

Objectives: Cerebral small vessel disease (SVD) is a common disease in patients with ischemic stroke and the most common cause of vascular dementia. Blood pressure (BP)-lowering is generally considered neuroprotective. Nevertheless, in patients with severe SVD burden, the optimal BP target is uncertain.

Hypothesis: BP-lowering to a systolic BP of 120-129mmHg in ischemic stroke patients with severe SVD is not associated with impaired cerebral perfusion, nor does it associate with worsening of structural connectivity and cognitive function.

Design and subjects: One-year trial where patients aged ≥50 with a history of ischaemic stroke and severe cerebral SVD will be randomised (1:1) to a systolic BP target of 120-129mmHg versus 130-140mmHg.

Study instruments: At baseline and one-year, all subjects will receive a brain magnetic resonance imaging (MRI) to evaluate their cerebral blood flow (CBF) and white matter integrity. They will also receive neuropsychological batteries to evaluate cognitive functioning. In addition, subjects will receive home BP monitoring with periodic medication changes prescribed by medical doctor to ensure the target BP is achieved.

Main outcome measures: Primary end-point is the change in CBF. Secondary end-points include changes in structural connectivity and cognitive performance.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Cerebral small vessel disease (SVD) is a common disease in patients with ischemic stroke and the most common cause of vascular dementia. The global burden of cerebral SVD is high and strategies to better prevent and manage cerebral SVD is urgently needed. Whilst blood pressure (BP) lowering is considered neuroprotective in patients with cerebral SVD, the optimal BP target in ischaemic stroke patients with severe SVD remains uncertain. Therefore, this randomised clinical trial aims to investigate whether two selected systolic blood pressure targets [systolic BP (SBP) 120-129mmHg versus 130-140mmHg] have different effects on cerebral blood flow and white matter integrity (structural connectivity) detected by magnetic resonance imaging (MRI) of the brain, as well as on cognition, over a one-year intervention period.

Chinese patients aged ≥50 with a prior history of TIA/ischaemic stroke fitting the inclusion and exclusion criteria will be recruited. At baseline, recruited subjects will undergo clinical and cognitive assessments. Blood pressure will be measured at clinic with an automated BP measurement system. A baseline non-contrast MRI of the brain will be arranged. The non-contrast MRI and cognitive assessments will be repeated at approximately 1 year after recruitment into the study.

To ensure consistency, our trial's antihypertensive strategy and titration shall align with those recommended by international guidelines. Blood tests for renal function will be arranged after modifying the prescription of specific anti-hypertensive agents (e.g. ACEis, ARBs, thiazide diuretics and spironolactone).

Study Type

Interventional

Enrollment (Anticipated)

104

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Gary KK LAU
  • Phone Number: 852-22554249
  • Email: gkklau@hku.hk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged ≥50
  2. Chinese ethnicity
  3. History of TIA/ischaemic stroke
  4. Underlying severe cerebral SVD as evidenced by brain MRI with total SVD score ≥3
  5. Underlying hypertension (defined as either SBP >140mmHg and taking no more than two anti-hypertensive agents, or SBP between 130-140mmHg and on at least one and not more than three anti-hypertensive agents)
  6. Able to provide written informed consent
  7. Able to perform study cognitive assessments
  8. Modified Rankin Scale (mRS) ≤3
  9. Expected life expectancy >2 years

Exclusion Criteria:

  1. Unable to, or unwilling to consent
  2. TIA/ischaemic stroke within three months (to avoid confounding effects of recovery on cognition from recent stroke)
  3. Brain MR angiogram showing significant symptomatic or asymptomatic carotid, vertebral or intracranial large artery stenosis ≥50% as measured using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria
  4. Cortical infarction >2cm in diameter
  5. Paroxysmal or permanent atrial fibrillation
  6. Known single gene disorder causing cerebral SVD, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
  7. Symptomatic postural hypotension
  8. Moderate- and severe-stage dementia with Montreal Cognitive Assessment (MOCA)-HK score <10
  9. Moderate and severe depressive symptoms with Patient Health Questionnaire-9 score ≥10
  10. Known secondary hypertension, e.g. hypertension is due to established obstructive sleep apnoea, renal parenchymal disease, renal artery stenosis, primary aldosteronism etc.
  11. Unable to complete cognitive assessments
  12. mRS >3
  13. Life expectancy of less than 2 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Intensive Treatment Group
SBP target 120-129 mmHg
Other: Intensive treatment
If the mean home SBP preceding clinic follow-up is >130mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <120mmHg, BP lowering treatment will be stepped down, until the target SBP of 120-129mmHg is achieved, or symptoms of hypotension prevent treatment to be further intensified.
Other: Standard Treatment Group
SBP target 130-140 mmHg
Other: Standard treatment
If the mean home SBP preceding clinic follow-up is >140mmHg, BP lowering treatment will be stepped up, and if the mean SBP preceding clinic follow-up is <130mmHg, BP lowering will be stepped down, until the target SBP 130-140mmg is achieved or symptoms of hypotension prevent treatment being intensified.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cerebral Blood Flow
Time Frame: From Baseline to approximate 1 year after recruitment
Change in whole-brain CBF as measured using MRI ASL at end of study (1 year) compared to baseline.
From Baseline to approximate 1 year after recruitment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grey Matter - Cerebral Blood Flow
Time Frame: From Baseline to approximate 1 year after recruitment
Change in Grey Matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.
From Baseline to approximate 1 year after recruitment
White Matter - Cerebral Blood Flow
Time Frame: From Baseline to approximate 1 year after recruitment
Change in white matter CBF as measured using MRI ASL at end of study (1 year) compared to baseline.
From Baseline to approximate 1 year after recruitment
Structural Connectivity
Time Frame: From Baseline to approximate 1 year after recruitment
Change in structural connectivity CBF as measured using MRI DTI at end of study (1 year) compared to baseline.
From Baseline to approximate 1 year after recruitment
Cognitive Function - MoCA
Time Frame: From Baseline to approximate 1 year after recruitment
Change in MoCA Score at end of study (1 year)
From Baseline to approximate 1 year after recruitment
Cognitive Function - Stroop colour-word test
Time Frame: From Baseline to approximate 1 year after recruitment
Change in Stroop colour-word test Score at end of study (1 year)
From Baseline to approximate 1 year after recruitment
Cognitive Function - Digit Symbol Coding test
Time Frame: From Baseline to approximate 1 year after recruitment
Change in Digital Symbol Coding test Score at end of study (1 year)
From Baseline to approximate 1 year after recruitment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Gary KK Lau, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2023

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

January 10, 2023

First Submitted That Met QC Criteria

January 10, 2023

First Posted (Estimate)

January 19, 2023

Study Record Updates

Last Update Posted (Estimate)

January 19, 2023

Last Update Submitted That Met QC Criteria

January 10, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GL2021001
  • UW21-128 (Other Identifier: HKU/HA HKW IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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