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: Recruiting

Sponsored by: National Institute on Aging (NIA)

Official(s) and/or principal investigator(s):
Ihab Hajjar, MD, Principal Investigator, Affiliation: Hebrew SeniorLife

Overall contact:
Meaghan Hart, Phone: 617-363-8484, Email: MeaghanHart@hrca.harvard.edu

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: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: Cognitive assessment measured by Trail Making Test, Hopkins Verbal Learning Test - Revised (HVLT-R), and Digit Span Test

Secondary outcome:

Changes in Cerebral Blood Flow (CBF) and cerebral vasoreactivity

Endothelial function assessed using the flow mediated dilatation (FMD) procedure

Biochemical measurement to monitor for adverse events: hyperkalemia, renal failure, leukopenia and liver function abnormalities

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) 6 months treatment with candesartan (ARB) compared to hydrochlorothiazide (HCTZ) and (ii) 6 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

- Uncontrolled 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

- Blood pressure greater than 200/110 if not on treatment or 180/100 mm Hg if on

antihypertensive therapy

- Mini-Mental-Status-Examination (MMSE) less than 20 or a clinical diagnosis of dementia

or Alzheimer's disease

- Elevated serum Creatinine above 2. 0 mg/dl or serum potassium above 5. 2 meq/dl or

higher

- Controlled hypertension less than 140/90 during the screening phase

- Receiving more than 2 antihypertensives

- History of congestive heart failure defined as active shortness of breath with minimal

exertion or evidence of volume overload

- History of diabetes mellitus defined as elevated blood sugar >126 mg/dl fasting or

>=200 random or receiving diabetes treatment

- History of stroke (less than 5 years)

- Permanent pacemaker (interferes with the neurovascular assessments)

- Inability by to perform the study procedures

Meaghan Hart, Phone: 617-363-8484, Email: MeaghanHart@hrca.harvard.edu

Institute for Aging Research at Hebrew SeniorLife, Boston, Massachusetts 02131, United States; Recruiting
Meaghan Hart, Phone: 617-363-8484, Email: MeaghanHart@hrca.harvard.edu
Ihab Hajjar, MD, MS, Principal Investigator
Lewis Lipsitz, MD, Sub-Investigator

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.

Waldstein SR, Katzel LI. Gender differences in the relation of hypertension to cognitive function in older adults. Neurol Res. 2004 Jul;26(5):502-6.

Pugh KG, Kiely DK, Milberg WP, Lipsitz LA. Selective impairment of frontal-executive cognitive function in african americans with cardiovascular risk factors. J Am Geriatr Soc. 2003 Oct;51(10):1439-44.

Kuo HK, Sorond F, Iloputaife I, Gagnon M, Milberg W, Lipsitz LA. Effect of blood pressure on cognitive functions in elderly persons. J Gerontol A Biol Sci Med Sci. 2004 Nov;59(11):1191-4.

Starting date: January 2008
Ending date: December 2011
Last updated: July 25, 2008