CAndesartan vs LIsinopril Effects on the BRain (CALIBREX)
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|ClinicalTrials.gov Identifier: NCT01984164|
Recruitment Status : Completed
First Posted : November 14, 2013
Last Update Posted : January 10, 2020
|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|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)|
|Study Start Date :||August 2014|
|Actual Primary Completion Date :||December 3, 2018|
|Actual Study Completion Date :||December 3, 2018|
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.
Other Name: Atacand
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.
- Executive function [ Time Frame: 12 months ]Executive function will be assessed using Trail Making Test (parts A, B and B-A) and the NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" tool box. This test battery reliably and validly assesses executive function in clinical trials [http://examiner.ucsf.edu/].
- Memory [ Time Frame: 12 months ]To assess memory we will use the Hopkins Verbal Learning Test (HVLT)
- Language [ Time Frame: 12 months ]This will be measured using the Boston Naming Test
- Attention [ Time Frame: 12 months ]This will be measured using Digit Span Forward/Backward
- White Matter Hyperintensity (WMH) Volume [ Time Frame: 12 months ]Structural MRI and WMH: High-resolution anatomical images will be acquired to identify WMH volumes as a marker of microvascular brain injury.
- rs-fMRI [ Time Frame: 12 months ]Resting functional MRI (r-fMRI): This protocol assesses the communication or "functional connectivity" between brain regions. Functional connectivity has a key role in important complex cognitive processes. It focuses on spontaneous, rather than task-induced, low frequency (<0.1 Hz) fluctuations in the blood oxygenation level-dependent (BOLD) signals.
- Cerebral Perfusion and Vasoreactivity (VR) [ Time Frame: 12 months ]ASL-MRI: Arterial Spin Labeling (ASL)MRI will be used to obtain perfusion measures in the brain. BOLD MRI Images will be acquired during normocapnia and hypercapnia
- Carotid intima-media thickness (CIMT) [ Time Frame: 12 months ]High-resolution B-mode ultrasonograms of the right common carotid artery will be obtained to assess the degree of atherosclerosis.
- Endothelial Progenitor Cells [ Time Frame: 12 months ]Endothelial progenitor cells (EPC) will also be collected.
- Arterial Stiffness [ Time Frame: 12 months ]This will be assessed using Pulse Wave Velocity, PWV
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
|United States, Georgia|
|Atlanta, Georgia, United States, 30329|
|Principal Investigator:||Ihab Hajjar, MD, MS||Emory Univeristy|