Clinical trial NCT00605072: The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial
Official title: The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cognitive Impairment
Hypertension
Aging
Keywords: cognitive disorders
angiotensin receptor blockers
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Hebrew SeniorLife
First posted: 2008-01-30
Enrollment: 53
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Cognitive Assessment: Trail Making Test Part B
timeFrame: Baseline-12 months
measure: Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall
timeFrame: Baseline-12 months
measure: Cognitive Assessment: Forward Digit Span Test
timeFrame: Baseline-12 months
Secondary outcomes:
measure: Blood Pressure Outcome: Systolic BP
timeFrame: Baseline-12 months
measure: Blood Flow Velocity, Sitting
timeFrame: Baseline-12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Boston
country: United States
facility: Hebrew SeniorLife
state: Massachusetts
Study officials:
affiliation: University of Southern California
name: Ihab Hajjar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1161/01.HYP.0000153094.09615.11. Epub 2005 Jan 17.
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.
citation: 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: 10.1001/archinternmed.2011.1391. No abstract available.
citation: Hajjar I, Hart M, Chen YL, Mack W, Novak V, C Chui H, Lipsitz L. Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial. J Am Geriatr Soc. 2013 Feb;61(2):194-201. doi: 10.1111/jgs.12100. Epub 2013 Jan 25.