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CAndesartan vs LIsinopril Effects on the BRain (CALIBREX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01984164
Recruitment Status : Completed
First Posted : November 14, 2013
Last Update Posted : January 10, 2020
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Ihab Hajjar, Emory University

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

Detailed Description:
  • 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.

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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)
Study Start Date : August 2014
Actual Primary Completion Date : December 3, 2018
Actual Study Completion Date : December 3, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Candesartan
blinded
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.
Drug: Lisinopril
Blinded




Primary Outcome Measures :
  1. 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/].


Secondary Outcome Measures :
  1. Memory [ Time Frame: 12 months ]
    To assess memory we will use the Hopkins Verbal Learning Test (HVLT)

  2. Language [ Time Frame: 12 months ]
    This will be measured using the Boston Naming Test

  3. Attention [ Time Frame: 12 months ]
    This will be measured using Digit Span Forward/Backward

  4. 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.

  5. 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.

  6. 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


Other Outcome Measures:
  1. 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.

  2. Endothelial Progenitor Cells [ Time Frame: 12 months ]
    Endothelial progenitor cells (EPC) will also be collected.

  3. Arterial Stiffness [ Time Frame: 12 months ]
    This will be assessed using Pulse Wave Velocity, PWV



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. age: 55 years or older;
  2. Hypertension: SBP≥140 mm Hg or DBP≥ 90 mm or receiving antihypertensive medications.
  3. Executive MCI will be defined using these criteria:

    1. The Montreal Cognitive Assessment (MoCA) score less than or equal to 26
    2. 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.
    3. Minimal Functional limitation as reflected by the Functional Assessment Questionnaire (FAQ)≤7

Exclusion Criteria:

  1. Intolerance to study drugs;
  2. SBP >200 or DBP >110 mm Hg;
  3. Renal disease or hyperkalemia
  4. Active medical or psychiatric problems
  5. Uncontrolled congestive heart failure;
  6. History of stroke in the past 3 years;
  7. Inability to perform the study procedures
  8. Women of childbearing potential
  9. diagnosis of dementia
  10. 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
  11. 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
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United States, Georgia
Emory Univeristy
Atlanta, Georgia, United States, 30329
Sponsors and Collaborators
Emory University
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Ihab Hajjar, MD, MS Emory Univeristy
  Study Documents (Full-Text)

Documents provided by Ihab Hajjar, Emory University:
Informed Consent Form  [PDF] October 12, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Last Update Posted: January 10, 2020
Last Verified: January 2020

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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:
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