The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00605072

Acronym

AVEC

Enrollment

Registered

2008-01-30

Start date

2008-01-31

Completion date

2012-12-31

Last updated

2013-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aging, Cognitive Impairment, Hypertension

Keywords

cognitive disorders, angiotensin receptor blockers

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.

Interventions

DRUGcandesartan

orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months

DRUGlisinopril

orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months

DRUGhydrochlorothiazide

orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months

DRUGnifedipine, long acting

If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments

DRUGmetoprolol, long-acting

If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
ACEI (Lisinopril) Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg	18
ARB (Candesartan) Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg	20
HCTZ hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months nifedipine, long acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 30 mg increased to 60 mg and 90 mg in 2 week increments metoprolol, long-acting : If needed to achieve target blood pressure of 140/90, added to ARB or ACEI at 12.5 mg increased to 25 mg and 50 mg	15
Total	53

Baseline characteristics

Characteristic	ACEI (Lisinopril)	ARB (Candesartan)	HCTZ	Total
Age Continuous	71 years STANDARD_DEVIATION 7	71 years STANDARD_DEVIATION 9	71 years STANDARD_DEVIATION 7	71 years STANDARD_DEVIATION 7
Region of Enrollment United States	18 participants	20 participants	15 participants	53 participants
Sex: Female, Male Female	11 Participants	11 Participants	9 Participants	31 Participants
Sex: Female, Male Male	7 Participants	9 Participants	6 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	5 / 18	6 / 20	6 / 15
serious Total, serious adverse events	0 / 18	0 / 20	0 / 15

Outcome results

Primary

Cognitive Assessment: Forward Digit Span Test

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)