CAndesartan vs LIsinopril Effects on the BRain (CALIBREX)
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| ClinicalTrials.gov Identifier: NCT01984164 |
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Recruitment Status :
Completed
First Posted : November 14, 2013
Results First Posted : February 21, 2021
Last Update Posted : February 21, 2021
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Sponsor:
Emory University
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Ihab Hajjar, Emory University
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypertension Mild Cognitive Impairment | Drug: Candesartan Drug: Lisinopril | Phase 2 |
- Hypertension is associated with cognitive impairment even in the absence of clinical dementia. To date, no specific treatment is available for this pattern of mild cognitive impairment related to hypertension.
- Objectives or purpose: The aims of this study are to investigate the effects of candesartan on executive function decline and on changes in cerebral perfusion, cerebrovascular reserve and microvascular brain injury. The study also intends to identify potential underlying mechanisms related to vascular structure and function, including atherosclerosis, vascular inflammation, vascular stiffness, and endothelial progenitor cells, by which candesartan may affect the cognitive and cerebrovascular outcomes.
- Study methodology:This is a double blind randomized clinical trial that will be conducted in 140 individuals (70 in the candesartan group, 70 in the lisinopril group). Our target population is subjects: 55 years or older with hypertension and Executive Mild Cognitive Impairment.
- Endpoints to be measured:Our measures include cognitive function, cerebral perfusion and reserve, markers of vascular brain damage, atherosclerosis, stiffness, vascular inflammation and endothelial function.
- Description of intervention, follow-up, and duration of study: Eligible participants will undergo randomization into 2 groups and will be seen frequently until their blood pressure is controlled (<140/90 mmHg). Participants will be seen at 3, 6 and 12 months afterwards.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 176 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX) |
| Actual Study Start Date : | August 20, 2014 |
| Actual Primary Completion Date : | December 3, 2018 |
| Actual Study Completion Date : | December 3, 2018 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hypertension
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 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.
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Drug: Candesartan
blinded
Other Name: Atacand |
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Active Comparator: 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.
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Drug: Lisinopril
Blinded |
Primary Outcome Measures :
- Executive Function [ Time Frame: 12 months ]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.
- NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box. [ Time Frame: 12 months ]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)
Secondary Outcome Measures :
- Memory [ Time Frame: 12 months ]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.
- Language [ Time Frame: 12 months ]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.
- Attention Measured Using Digit Span Backward [ Time Frame: 12 months ]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.
- White Matter Lesion Volume [ Time Frame: 12 months ]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
- Cerebral Perfusion [ Time Frame: 12 months ]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.
- Attention Measured Using Digit Span Forward [ Time Frame: 12 months ]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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 55 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- age: 55 years or older;
- Hypertension: SBP≥140 mm Hg or DBP≥ 90 mm or receiving antihypertensive medications.
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Executive MCI will be defined using these criteria:
- The Montreal Cognitive Assessment (MoCA) score less than or equal to 26
- Executive dysfunction: A performance at the 10th percentile or below on at least one of four screening tests for executive function: Trail Making Test, Part B (TMT-B), modified Stroop interference, Digit Span and Digit Sequencing, and Letter fluency.
- Minimal Functional limitation as reflected by the Functional Assessment Questionnaire (FAQ)≤7
Exclusion Criteria:
- Intolerance to study drugs;
- SBP >200 or DBP >110 mm Hg;
- Renal disease or hyperkalemia
- Active medical or psychiatric problems
- Uncontrolled congestive heart failure;
- History of stroke in the past 3 years;
- Inability to perform the study procedures
- Women of childbearing potential
- diagnosis of dementia
- In those who lack decision capacity, a study surrogate who can sign on their behalf will be required. Since we are enrolling only those with MCI, we anticipate that most participants will have decision capacity
- Current use of Lithium, as most antihypertensive classes may lead to increased lithium toxic levels.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01984164
Locations
| United States, Georgia | |
| Emory Univeristy | |
| Atlanta, Georgia, United States, 30329 | |
Sponsors and Collaborators
Emory University
National Institute on Aging (NIA)
Investigators
| Principal Investigator: | Ihab Hajjar, MD, MS | Emory Univeristy |
Study Documents (Full-Text)
Documents provided by Ihab Hajjar, Emory University:
Documents provided by Ihab Hajjar, Emory University:
Informed Consent Form [PDF] October 12, 2017
Study Protocol and Statistical Analysis Plan [PDF] February 5, 2015
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ihab Hajjar, Principal Investigator, Emory University |
| ClinicalTrials.gov Identifier: | NCT01984164 |
| Other Study ID Numbers: |
IRB00070087 R01AG042127 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 14, 2013 Key Record Dates |
| Results First Posted: | February 21, 2021 |
| Last Update Posted: | February 21, 2021 |
| Last Verified: | February 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by Ihab Hajjar, Emory University:
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Cerebrovascular function |
Additional relevant MeSH terms:
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Cognitive Dysfunction Cognition Disorders Neurocognitive Disorders Mental Disorders Candesartan Lisinopril Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers |
Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Cardiotonic Agents Protective Agents Physiological Effects of Drugs |