The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

Condition(s) targeted: Cognitive Impairment; Hypertension; Aging

Intervention: candesartan (Drug); lisinopril (Drug); hydrochlorothiazide (Drug); nifedipine, long acting (Drug); metoprolol, long-acting (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University of Southern California

Official(s) and/or principal investigator(s):
Ihab Hajjar, MD, Principal Investigator, Affiliation: University of Southern California

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.

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

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

Primary outcome:

Cognitive Assessment: Trail Making Test Part B

Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall

Cognitive Assessment: Forward Digit Span Test

Secondary outcome:

Blood Pressure Outcome: Systolic BP

Blood Flow Velocity, Sitting

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.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

University of Southern California, Los Angeles, California 90033, United States

Hebrew SeniorLife, Boston, Massachusetts 02131, United States

Related publications:

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.

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.

Starting date: January 2008
Last updated: January 14, 2013