The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

Hypertension Clinical Trial

— AVEC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00605072
• Other study ID #: IA0127
• Secondary ID: K23AG030057
• Status: Completed
• Phase: Phase 2
• First received: January 11, 2008
• Last updated: January 14, 2013
• Start date: January 2008
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aging
• Cognition Disorders
• Cognitive Impairment
• Hypertension

Intervention

Drug:
• candesartan
orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months
• lisinopril
orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months
• 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

Locations

Country	Name	City	State
United States	Hebrew SeniorLife	Boston	Massachusetts
United States	University of Southern California	Los Angeles	California

Sponsors (3)

Lead Sponsor	Collaborator
University of Southern California	Hebrew SeniorLife, National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Hajjar I, Hart M, Chen YL, Mack W, Milberg W, Chui H, Lipsitz L. Effect of antihypertensive therapy on cognitive function in early executive cognitive impairment: a double-blind randomized clinical trial. Arch Intern Med. 2012 Mar 12;172(5):442-4. doi: 10 — View Citation

Hajjar I, Hart M, Milberg W, Novak V, Lipsitz L. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: role of the renin angiotensin system inhibition. BMC Geriatr. 2009 Nov 18;9:48. doi: 10.1186/1471-2318-9-48. — View Citation

Lipsitz LA, Gagnon M, Vyas M, Iloputaife I, Kiely DK, Sorond F, Serrador J, Cheng DM, Babikian V, Cupples LA. Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects. Hypertension. 2005 Feb;45(2):216-21. Epub 2005 Jan 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Assessment: Trail Making Test Part B	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.	Baseline-12 months	No
Primary	Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall	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)	Baseline-12 months	No
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)	Baseline-12 months	No
Secondary	Blood Pressure Outcome: Systolic BP	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	Baseline-12 months	No
Secondary	Blood Flow Velocity, Sitting	This reports the change in the least square mean from baseline to 12 months, adjusted for age	Baseline-12 months	No