The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

Phase 2

Completed

• Conditions: Cognitive Impairment; Hypertension; Aging
• Interventions: Drug: hydrochlorothiazide; Drug: candesartan; Drug: lisinopril; Drug: nifedipine, long acting; Drug: metoprolol, long-acting

• Registration Number: NCT00605072
• Lead Sponsor: University of Southern California

Brief Summary

The purpose of this study is to examine the effects of blood pressure medications on cognition and blood flow in hypertensive elderly patients with cognitive impairment. The hypothesis is that treatment with an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEI) will be associated with a slower rate of further cognitive decline, improved cerebral blood flow and its regulation, and preserved physical function as compared to treatment with a diuretic (HCTZ), independent of blood pressure level.

Detailed Description

There is mounting evidence that hypertension, which affects more than 65% of the US elderly population, accelerates cognitive decline and increases the risk of functional disability among older individuals. Hypertension is also associated with cerebral blood flow reduction and dysregulation which contribute to further cognitive and functional impairment. Drugs that inhibit angiotensin II (ACEI and ARB) are commonly used antihypertensives and may have a protective effect on cognitive function, cerebral blood flow and physical function compared to other antihypertensives such as hydrochlorothiazide (HCTZ).

A total of 100 individuals will be recruited for this pilot 3-arm randomized study to investigate the effects of: (i) 12 months treatment with candesartan (ARB) compared to hydrochlorothiazide (HCTZ) and (ii) 12 months treatment with lisinopril (ACEI) compared to HCTZ and (iii) to estimate the effect size difference between lisinopril and losartan on cognition, cerebral blood flow regulation, and functional measures in a sample of elderly hypertensive individuals with objective evidence of cognitive impairment.

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-01-11
• Study First Submitted QC: 2008-01-17
• Study First Posted: 2008-01-30
• Primary Completion: 2011-12
• Study Completion: 2012-12
• Results First Submitted: 2012-12-04
• Status Verified: 2013-01
• Results First Submitted QC: 2013-01-14
• Last Update Submitted: 2013-01-14
• Results First Posted: 2013-02-15
• Last Update Posted: 2013-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

• 60 years or older
• Hypertension
• Cognitive criteria: score either 10 or less out of 15 for the executive clock draw test 1 (CLOX1) or less than or equal to 1 standard deviation from the corresponding age specific mean on the immediate memory subtest

Exclusion Criteria

• Intolerance to ACEI or ARB
• History of congestive heart failure
• History of diabetes mellitus
• History of stroke (less than 6 months)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Candesartan	nifedipine, long acting	Angiotensin Receptor Blocker
Candesartan	metoprolol, long-acting	Angiotensin Receptor Blocker
Lisinopril	nifedipine, long acting	Angiotensin-Converting Enzyme (ACE) Inhibitor
Lisinopril	metoprolol, long-acting	Angiotensin-Converting Enzyme (ACE) Inhibitor
HCTZ	hydrochlorothiazide	Hydrochlorothiazide (diuretic)
Candesartan	candesartan	Angiotensin Receptor Blocker
Lisinopril	lisinopril	Angiotensin-Converting Enzyme (ACE) Inhibitor

Primary Outcome Measures

Name	Time	Method
Cognitive Assessment: Trail Making Test Part B	Baseline-12 months	This test requires the connection of sequentially numbered circles (A), and the connection of circles marked by numbers and letters in alternating sequence (B). This test is considered a benchmark of executive function. The test score is the time required to complete the task in seconds.
Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall	Baseline-12 months	This is a 12-item list learning test in which individuals are presented three learning and recall trials followed by a delayed recall and 24 item recognition test. The HVLT-R has been identified as an ideal memory measure for elderly patients, and appropriate reliability and validity have been shown in older individuals. The test score is the number of correct answers in the delayed recall ( score range 0-12)
Cognitive Assessment: Forward Digit Span Test	Baseline-12 months	This test consists of series of digits of increasing length, some of which are recited as presented, and some of which are to be recited in reversed order. The forward digit span score ranges from 0 (ie cannot repeat two digits) to 8 ( participant can repeat up to 8 digits)

Secondary Outcome Measures

Name	Time	Method
Blood Pressure Outcome: Systolic BP	Baseline-12 months	Blood pressure was measured as follows: the participant was in the sitting position, rested for 5 minutes, no caffeine or smoking 2 hours prior to measurement, using appropriate cuff size (covering 60% of upper arm length and 80% of arm circumference), correct cuff placement (1-2 inches above brachial pulse on bare arm), and the bell of the stethoscope. The systolic blood pressure was defined as the pressure corresponding to the first korotkoff sounds (K1) and the diastolic as the pressure corresponding to the last korotkoff sound (K5). Blood pressure was measured in both arms and recorded
Blood Flow Velocity, Sitting	Baseline-12 months	This reports the change in the least square mean from baseline to 12 months, adjusted for age

Trial Locations

Locations (2)

Hebrew SeniorLife; 🇺🇸 Boston, Massachusetts, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States