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| ID | Type | Description | Link |
|---|---|---|---|
| K23AG030057 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Hebrew SeniorLife | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Candesartan | Experimental | Angiotensin Receptor Blocker |
|
| Lisinopril | Experimental | Angiotensin-Converting Enzyme (ACE) Inhibitor |
|
| HCTZ | Active Comparator | Hydrochlorothiazide (diuretic) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| candesartan | Drug | orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Assessment: Trail Making Test Part B | 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. | Baseline-12 months |
| Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall | 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) | Baseline-12 months |
| Cognitive Assessment: Forward Digit Span Test | 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) | Baseline-12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Pressure Outcome: Systolic BP | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ihab Hajjar, MD | University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California | Los Angeles | California | 90033 | United States | ||
| Hebrew SeniorLife |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15655124 | Background | 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. | |
| 19922631 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lisinopril | Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| FG001 | Candesartan | Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| FG002 | HCTZ | hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ACEI (Lisinopril) | Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cognitive Assessment: Trail Making Test Part B | 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. | Posted | Least Squares Mean | Standard Error | seconds | Baseline-12 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ACEI (Lisinopril) | Angiotensin-Converting Enzyme (ACE) Inhibitor: lisinopril : orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | Systematic Assessment |
The main limitation is the small sample size. The validity of TCD measurements as an index of cerebral blood flow is based on the assumption that cerebral vessel diameters are constant but we didn't have brain imaging to validate this assumption.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ihab Hajjar | University of Southern California | 323-226-6720 | ihajjar@usc.edu |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C081643 | candesartan |
| C077793 | candesartan cilexetil |
| D017706 | Lisinopril |
| D006852 | Hydrochlorothiazide |
| D009543 | Nifedipine |
| D008790 | Metoprolol |
| ID | Term |
|---|---|
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| lisinopril | Drug | orally 10 mg increased to 20 mg then 40 mg to achieve target blood pressure of 140/90, then daily for 12 months |
|
|
| hydrochlorothiazide | Drug | orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months |
|
|
| nifedipine, long acting | Drug | 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 |
|
|
| metoprolol, long-acting | Drug | 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 |
|
|
| Baseline-12 months |
| Blood Flow Velocity, Sitting | This reports the change in the least square mean from baseline to 12 months, adjusted for age | Baseline-12 months |
| Boston |
| Massachusetts |
| 02131 |
| United States |
| 22412114 | Result | 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. |
| 23350899 | Derived | 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. |
| BG001 | ARB (Candesartan) | Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| BG002 | HCTZ | hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | ARB (Candesartan) | Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
| OG002 | HCTZ | hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 |
|
|
|
| Secondary | Blood Pressure Outcome: Systolic BP | 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 | Posted | Least Squares Mean | Standard Error | mm Hg | Baseline-12 months |
|
|
|
|
| Secondary | Blood Flow Velocity, Sitting | This reports the change in the least square mean from baseline to 12 months, adjusted for age | Posted | Least Squares Mean | Standard Error | cm/sec | Baseline-12 months |
|
|
|
|
| Primary | Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall | 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) | Posted | Least Squares Mean | Standard Error | number words remembered | Baseline-12 months |
|
|
|
|
| Primary | Cognitive Assessment: Forward Digit Span Test | 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) | Posted | Least Squares Mean | Standard Error | number of digits repeated | Baseline-12 months |
|
|
|
|
| 0 |
| 18 |
| 5 |
| 18 |
| EG001 | ARB (Candesartan) | Angiotensin Receptor Blocker: candesartan : orally 8 mg increased to 16 mg then 32 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 | 0 | 20 | 6 | 20 |
| EG002 | HCTZ | hydrochlorothiazide : orally 12.5 mg increased to 25 mg to achieve target blood pressure of 140/90, then daily for 12 months 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 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 | 0 | 15 | 6 | 15 |
| Weakness or Fatigue | Nervous system disorders |
|
| Fall, non-injurious | Nervous system disorders |
|
| Cough | Respiratory, thoracic and mediastinal disorders |
|
| Hospitalization (non-elective) | Injury, poisoning and procedural complications |
|
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| D002318 |
| Cardiovascular Diseases |
| D002740 |
| Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D020005 | Propanols |
| D000588 | Amines |