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

This study has been completed.
Sponsor:
Collaborators:
Hebrew SeniorLife
Information provided by (Responsible Party):
Ihab Hajjar, University of Southern California
ClinicalTrials.gov Identifier:
NCT00605072
First received: January 11, 2008
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Cognitive Impairment
Hypertension
Aging
Drug: candesartan
Drug: lisinopril
Drug: hydrochlorothiazide
Drug: nifedipine, long acting
Drug: metoprolol, long-acting
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial)

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Cognitive Assessment: Trail Making Test Part B [ Time Frame: Baseline-12 months ] [ Designated as safety issue: No ]
    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.

  • Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall [ Time Frame: Baseline-12 months ] [ Designated as safety issue: No ]
    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)

  • Cognitive Assessment: Forward Digit Span Test [ Time Frame: Baseline-12 months ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Blood Pressure Outcome: Systolic BP [ Time Frame: Baseline-12 months ] [ Designated as safety issue: No ]
    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

  • Blood Flow Velocity, Sitting [ Time Frame: Baseline-12 months ] [ Designated as safety issue: No ]
    This reports the change in the least square mean from baseline to 12 months, adjusted for age


Enrollment: 53
Study Start Date: January 2008
Study Completion Date: December 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Candesartan
Angiotensin Receptor Blocker
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
Other Name: Atacand
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
Other Name: Procardia XL
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
Other Name: Lopressor, Toprol XL
Experimental: Lisinopril
Angiotensin-Converting Enzyme (ACE) Inhibitor
Drug: lisinopril
orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months
Other Name: Prinivil
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
Other Name: Procardia XL
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
Other Name: Lopressor, Toprol XL
Active Comparator: HCTZ
Hydrochlorothiazide (diuretic)
Drug: hydrochlorothiazide
orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months
Other Name: HCTZ, multiple brand names

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

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00605072

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033
United States, Massachusetts
Hebrew SeniorLife
Boston, Massachusetts, United States, 02131
Sponsors and Collaborators
University of Southern California
Hebrew SeniorLife
Investigators
Principal Investigator: Ihab Hajjar, MD University of Southern California
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ihab Hajjar, Assistant Professor of Medicine, University of Southern California
ClinicalTrials.gov Identifier: NCT00605072     History of Changes
Other Study ID Numbers: IA0127, K23AG030057
Study First Received: January 11, 2008
Results First Received: December 4, 2012
Last Updated: January 14, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of Southern California:
cognitive disorders
angiotensin receptor blockers

Additional relevant MeSH terms:
Cognition Disorders
Hypertension
Cardiovascular Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Vascular Diseases
Angiotensin Receptor Antagonists
Antihypertensive Agents
Candesartan
Candesartan cilexetil
Hydrochlorothiazide
Lisinopril
Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Cardiotonic Agents
Cardiovascular Agents
Diuretics
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Protective Agents
Sodium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014