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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG042127 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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The aim of this study is to conduct a 1-year double blind randomized control trial comparing candesartan to lisinopril in 140 individuals with hypertension and executive mild cognitive impairment in their effects on executive function, neuroimaging markers, and vascular indicators.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Candesartan | Active Comparator | To achieve blood pressure control, we will use a stepwise protocol as follows: candesartan (blinded) 8mg→ 16mg→ 32mg. Both groups will also receive (unblinded) , if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg →10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. |
|
| Lisinopril | Active Comparator | To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Candesartan | Drug | blinded |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Executive Function | Executive function will be assessed using Trail Making Test (part B-A). Part A was collected to correct for motor speed and visual-perceptual demands on TMT by subtracting completion time for TMT Part A from completion time for Part B (TMT B - A). TMT Part B-A provides a relatively purer measure of executive functioning. It has a timed scale from 0 sec (min) to 300 secs (max). Along this scale, a lower score is better. | 12 months |
| NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box. | EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" tool box. This test batteryThe battery includes 11 tasks that generate 15 primary variables. Within this set, the EXAMINER includes: working memory, inhibition, set shifting, and fluency. The parts of EXAMINER that were used for this study include: Flanker task (inhibition) which involves responding to a central stimulus while ignoring flanking stimuli that are either compatible or incompatible with the central stimulus; Set-shifting, a measure of mental flexibility; Spatial 1-Back test assesses spatial working memory; Dot Counting test assesses verbal working memory; Verbal Fluency tested using a List Generation test which require the participant to generate words beginning with a specific letter, and category fluency in which the participant generates words from a specified category (e.g., animals, fruits). Higher are reflective of better executive function (-1 to +1) | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Memory | To assess episodic memory, the Hopkins Verbal Learning Test-Revised (HVLT-R) will be used. The retention (%) score is calculated by dividing the delayed recall trial by the higher of 3 learning trials. Each trial scores 0 (min) to 12 (max). The HVLT-R retention score is a percentage, and a higher percentage represents a better outcome. | 12 months |
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Inclusion Criteria:
age: 55 years or older;
Hypertension: SBP≥140 mm Hg or DBP≥ 90 mm or receiving antihypertensive medications.
Executive MCI will be defined using these criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ihab Hajjar, MD, MS | Emory Univeristy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Univeristy | Atlanta | Georgia | 30329 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32761160 | Derived | Hajjar I, Okafor M, McDaniel D, Obideen M, Dee E, Shokouhi M, Quyyumi AA, Levey A, Goldstein F. Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Netw Open. 2020 Aug 3;3(8):e2012252. doi: 10.1001/jamanetworkopen.2020.12252. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Candesartan | To achieve blood pressure control, we will use a stepwise protocol as follows: candesartan (blinded) 8mg→ 16mg→ 32mg. Both groups will also receive (unblinded) , if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg →10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Candesartan: blinded |
| FG001 | Lisinopril | To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Lisinopril: Blinded |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Candesartan | To achieve blood pressure control, we will use a stepwise protocol as follows: candesartan (blinded) 8mg→ 16mg→ 32mg. Both groups will also receive (unblinded) , if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg →10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Candesartan: blinded |
| 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 | Executive Function | Executive function will be assessed using Trail Making Test (part B-A). Part A was collected to correct for motor speed and visual-perceptual demands on TMT by subtracting completion time for TMT Part A from completion time for Part B (TMT B - A). TMT Part B-A provides a relatively purer measure of executive functioning. It has a timed scale from 0 sec (min) to 300 secs (max). Along this scale, a lower score is better. | Posted | Least Squares Mean | Standard Error | seconds | 12 months |
|
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 | Candesartan | To achieve blood pressure control, we will use a stepwise protocol as follows: candesartan (blinded) 8mg→ 16mg→ 32mg. Both groups will also receive (unblinded) , if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg →10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Candesartan: blinded |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
A limitation of this study is its 1-year study period. Additional limitations include the relatively small sample size, which limited our power to correct for multiple comparisons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hajjar | Emory University | 404-712-2036 | ihabhajjar@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Oct 12, 2017 | Jun 18, 2019 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 5, 2015 | Oct 20, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| C081643 | candesartan |
| C077793 | candesartan cilexetil |
| D017706 | Lisinopril |
| ID | Term |
|---|---|
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Lisinopril |
| Drug |
Blinded |
|
| Language | This will be measured using the Boston Naming Test. BNT is a neuropsychological test used to assess visual confrontation naming and language performance in participants with cognitive decline. Its short 15-item version consists of drawings of objects ranging from common objects to less familiar objects. Scale: 0 (min score) to 15 (max score). For this test, a higher score/response represents a better outcome. | 12 months |
| Attention Measured Using Digit Span Backward | The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span backwards, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in reverse order (backward span). Backward span is an executive task particularly dependent on working memory. The Digit Span backward is scored for backwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome. | 12 months |
| White Matter Lesion Volume | White Matter Lesion volume: high-resolution anatomical images are acquired for the measurement of microvascular disease. WMH volumes will be obtained from Fluid attenuated inversion recovery (FLAIR) imaging sequence and reported as total volume (in mm3). Higher values means greater WMH | 12 months |
| Cerebral Perfusion | ASL-MRI: Arterial Spin Labeling (ASL) MRI is non-invasive measure of perfusion that does not require contrast, and allows multiple brain regions mapping of perfusion and reserve. ASL-MRI provides measures of cerebral blood flow (CBF). Higher values indicates higher CBF. | 12 months |
| Attention Measured Using Digit Span Forward | This will be measured using Digit Span Forward. The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span forward, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in the correct order (forward span). Forward span captures attention efficiency and capacity. The Digit Span forward is scored for forwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome. | 12 months |
| Lost to Follow-up |
|
| BG001 | Lisinopril | To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Lisinopril: Blinded |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Of 176 eligible participants enrolled and randomized to candesartan or lisinopril, 35 dropped out before study completion (25 from the lisinopril arm and 10 from the candesartan arm). The final sample for the intention-to-treat analysis was 141 individuals, including 77 in the candesartan group and 64 in the lisinopril group. | Number | participants |
|
| MoCA score | MoCA is a 30-point scale administered in 10 minutes, is validated in Spanish and is highly sensitive to identify mild vascular-related cognitive dysfunction. MoCA includes assessment of MoCA assesses: Short term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language and orientation to time and place. Scale is 0-30 with higher indicated better cognitive performance. | Mean | Standard Deviation | points |
|
| OG001 | Lisinopril | To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Lisinopril: Blinded |
|
|
|
| Primary | NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box. | EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" tool box. This test batteryThe battery includes 11 tasks that generate 15 primary variables. Within this set, the EXAMINER includes: working memory, inhibition, set shifting, and fluency. The parts of EXAMINER that were used for this study include: Flanker task (inhibition) which involves responding to a central stimulus while ignoring flanking stimuli that are either compatible or incompatible with the central stimulus; Set-shifting, a measure of mental flexibility; Spatial 1-Back test assesses spatial working memory; Dot Counting test assesses verbal working memory; Verbal Fluency tested using a List Generation test which require the participant to generate words beginning with a specific letter, and category fluency in which the participant generates words from a specified category (e.g., animals, fruits). Higher are reflective of better executive function (-1 to +1) | Posted | Least Squares Mean | Standard Error | units on a scale | 12 months |
|
|
|
| Secondary | Memory | To assess episodic memory, the Hopkins Verbal Learning Test-Revised (HVLT-R) will be used. The retention (%) score is calculated by dividing the delayed recall trial by the higher of 3 learning trials. Each trial scores 0 (min) to 12 (max). The HVLT-R retention score is a percentage, and a higher percentage represents a better outcome. | Posted | Least Squares Mean | Standard Error | percentage of retention | 12 months |
|
|
|
| Secondary | Language | This will be measured using the Boston Naming Test. BNT is a neuropsychological test used to assess visual confrontation naming and language performance in participants with cognitive decline. Its short 15-item version consists of drawings of objects ranging from common objects to less familiar objects. Scale: 0 (min score) to 15 (max score). For this test, a higher score/response represents a better outcome. | Posted | Least Squares Mean | Standard Error | number of correct responses | 12 months |
|
|
|
| Secondary | Attention Measured Using Digit Span Backward | The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span backwards, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in reverse order (backward span). Backward span is an executive task particularly dependent on working memory. The Digit Span backward is scored for backwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome. | Posted | Least Squares Mean | Standard Error | Number of correct responses | 12 months |
|
|
|
| Secondary | White Matter Lesion Volume | White Matter Lesion volume: high-resolution anatomical images are acquired for the measurement of microvascular disease. WMH volumes will be obtained from Fluid attenuated inversion recovery (FLAIR) imaging sequence and reported as total volume (in mm3). Higher values means greater WMH | Of 176 randomized participants, 27 did not complete an MRI scan at baseline (15 had metal implants with either pacemaker, stent, or inferior vena cava filter and 12 were claustrophobic). Of 141 participants who returned for their 12-month visit, an additional 8 participants refused to have a follow-up MRI. The final sample with both baseline and 12-month MRI was 104 participants (73.8%), including 51 participants in the candesartan group and 53 participants in the lisinopril group. | Posted | Least Squares Mean | Standard Error | mm^3 | 12 months |
|
|
|
| Secondary | Cerebral Perfusion | ASL-MRI: Arterial Spin Labeling (ASL) MRI is non-invasive measure of perfusion that does not require contrast, and allows multiple brain regions mapping of perfusion and reserve. ASL-MRI provides measures of cerebral blood flow (CBF). Higher values indicates higher CBF. | Of 176 randomized participants, 27 did not complete an MRI scan at baseline (15 had metal implants with either pacemaker, stent, or inferior vena cava filter and 12 were claustrophobic). Of 141 participants who returned for their 12-month visit, an additional 8 participants refused to have a follow-up MRI. The final sample with both baseline and 12-month MRI was 104 participants (73.8%), including 51 participants in the candesartan group and 53 participants in the lisinopril group. | Posted | Least Squares Mean | Standard Error | ml/100g/min | 12 months |
|
|
|
| Secondary | Attention Measured Using Digit Span Forward | This will be measured using Digit Span Forward. The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span forward, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in the correct order (forward span). Forward span captures attention efficiency and capacity. The Digit Span forward is scored for forwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome. | Posted | Least Squares Mean | Standard Error | Number of correct responses | 12 months |
|
|
|
| 0 |
| 87 |
| 0 |
| 87 |
| 87 |
| 87 |
| EG001 | Lisinopril | To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved. Lisinopril: Blinded | 0 | 89 | 0 | 89 | 89 | 89 |
| Headache | General disorders | Non-systematic Assessment |
|
| Dizziness | General disorders | Non-systematic Assessment |
|
| Edema | General disorders | Non-systematic Assessment |
|
| General Pain | General disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Nasal/sinus drainage | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Palpitation | Cardiac disorders | Non-systematic Assessment |
|
| Frequent urination | Renal and urinary disorders | Non-systematic Assessment |
|
| Leg Cramps | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Insomnia | General disorders | Non-systematic Assessment |
|
| Runny nose | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Unusual bleeding or bruising | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Falling | General disorders | Non-systematic Assessment |
|
| Dry mouth | General disorders | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Non-systematic Assessment |
|
| Loss of appetite | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Severe elevation in systolic BP >200 mmHg | Vascular disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Sweating | General disorders | Non-systematic Assessment |
|
| Fainting | General disorders | Non-systematic Assessment |
|
| Worsening renal function (serum creatinine >2.5) | Renal and urinary disorders | Non-systematic Assessment |
|
| Low potassium (<3.0) | Metabolism and nutrition disorders | Non-systematic Assessment |
|
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| D001523 |
| Mental Disorders |