Official Title: “The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial)”

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.

Study Type: Interventional

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

Study Primary Completion Date: December 2011

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.

Intervention(s) in this Clinical Trial

• Drug: candesartan
  • orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 6 months
• Drug: lisinopril
  • orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 6 months
• Drug: hydrochlorothiazide
  • orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 6 months
• Drug: 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
• Drug: 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: ARB
  • Angiotensin Receptor Blocker
• Experimental: ACEI
  • Angiotensin-Converting Enzyme (ACE) Inhibitor
• Active Comparator: HCTZ

Primary Measures

• Cognitive assessment measured by Trail Making Test, Hopkins Verbal Learning Test - Revised (HVLT-R), and Digit Span Test
  • Time Frame: Baseline, 1 and 6 months
    Safety Issue?: No

Secondary Measures

• Changes in Cerebral Blood Flow (CBF) and cerebral vasoreactivity
  • Time Frame: Baseline, and 6 months after BP control
    Safety Issue?: No
• Endothelial function assessed using the flow mediated dilatation (FMD) procedure
  • Time Frame: Baseline, and 6 months after BP control
    Safety Issue?: No
• Biochemical measurement to monitor for adverse events: hyperkalemia, renal failure, leukopenia and liver function abnormalities
  • Time Frame: Baseline, 2-4 weeks, 2, 4, and 9 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 60 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Aging (NIA)

Overall Clinical Trial Officials and Contacts

Ihab Hajjar, MD Principal Investigator Hebrew SeniorLife  

Overall Contact: Meaghan Hart 617-363-8484 MeaghanHart@hrca.harvard.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00605072

Study ID Number: IA0127

ClinicalTrials.gov Identifier: NCT00605072

Health Authority: United States: Federal Government