The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial - Full Text View

Sponsors and Collaborators:	National Institute on Aging (NIA) Hebrew SeniorLife
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00605072

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 II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial)

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines High Blood Pressure

Drug Information available for: Hydrochlorothiazide Nifedipine Metoprolol Metoprolol Tartrate Lisinopril Metoprolol succinate Metoprolol fumarate CV 11974 Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in Cerebral Blood Flow (CBF) and cerebral vasoreactivity [ Time Frame: Baseline, and 6 months after BP control ] [ Designated as safety issue: No ]
Endothelial function assessed using the flow mediated dilatation (FMD) procedure [ Time Frame: Baseline, and 6 months after BP control ] [ Designated as 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	January 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
ARB: Experimental 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 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
ACEI: Experimental 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 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
HCTZ: Active Comparator	Drug: hydrochlorothiazide orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 6 months

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.

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
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

Contacts and Locations

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

Contacts

Contact: Meaghan Hart

617-363-8484

MeaghanHart@hrca.harvard.edu

Locations

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

Sponsors and Collaborators

National Institute on Aging (NIA)

Hebrew SeniorLife

Investigators

Principal Investigator:

Ihab Hajjar, MD

Hebrew SeniorLife

More Information

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.

Responsible Party:	Hebrew SeniorLife ( Ihab Hajjar, MD )
Study ID Numbers:	IA0127, 1K23AG30057-01A1
Study First Received:	January 11, 2008
Last Updated:	January 29, 2009
ClinicalTrials.gov Identifier:	NCT00605072 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

cognitive disorders

Study placed in the following topic categories:

Sodium Chloride Symporter Inhibitors
Diuretics
Lisinopril
Vascular Diseases
Cardiovascular Agents
Angiotensin II
Antihypertensive Agents
Metoprolol
Nifedipine
Hydrochlorothiazide
Cognition Disorders

Protease Inhibitors
Angiotensin II Type 1 Receptor Blockers
Candesartan cilexetil
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Metoprolol succinate
Candesartan
Angiotensin-Converting Enzyme Inhibitors
Dementia
Hypertension
Delirium

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Diuretics
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Mental Disorders
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Diseases
Lisinopril
Vascular Diseases
Enzyme Inhibitors

Cardiovascular Agents
Antihypertensive Agents
Hydrochlorothiazide
Protective Agents
Pharmacologic Actions
Cognition Disorders
Protease Inhibitors
Angiotensin II Type 1 Receptor Blockers
Delirium, Dementia, Amnestic, Cognitive Disorders
Natriuretic Agents
Candesartan
Hypertension

ClinicalTrials.gov processed this record on July 02, 2009