Trial record 2 of 2 for:    Antihypertensives and Vascular, Endothelial and Cognitive Function Trial

CAndesartan vs LIsinopril Effects on the BRain (CALIBREX)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ihab M. Hajjar, Emory University
ClinicalTrials.gov Identifier:
NCT01984164
First received: October 27, 2013
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Hypertension
Mild Cognitive Impairment
Drug: Candesartan
Drug: Lisinopril
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Executive function (EXAMINER score) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Executive function will be assessed using 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:
  • Perfusion and Vasoreactivity (VR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    ASL-MRI: Arterial Spin Labeling (ASL)MRI will be used to obtain perfusion measures in the brain. Images will be acquired during normocapnia , hypercapnia, and hypocapnia.

  • rs-fMRI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Memory [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To assess memory we will use the California Verbal Learning Test

  • White Matter Hyperintensity (WMH) Volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Structural MRI and WMH: High-resolution anatomical images will be acquired to identify WMH volumes as a marker of microvascular brain injury.

  • Carotid intima-media thickness (CIMT) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Endothelial progenitor cells (EPC) will also be collected.


Estimated Enrollment: 140
Study Start Date: July 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Lisinopril

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: 60 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.
  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age: 60 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 26
    2. Clinical Dementia Rating (CDR) score of 0.5,
    3. 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, verbal fluency (number of D words in 1 minute), or abstractions.

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. Use of acetylcholine-esterase inhibitors or NMDA receptor antagonist (memantine)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01984164

Contacts
Contact: Ihab Hajjar, MD, MS 4047286959 ihajjar@emory.edu

Locations
United States, Georgia
Emory Univeristy Not yet recruiting
Atlanta, Georgia, United States, 30329
Contact: Ihab Hajjar, MD    404-728-6959    ihajjar@emory.edu   
Sponsors and Collaborators
Ihab M. Hajjar
Investigators
Principal Investigator: Ihab Hajjar, MD, MS Emory Univeristy
  More Information

No publications provided

Responsible Party: Ihab M. Hajjar, Prinicipal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01984164     History of Changes
Other Study ID Numbers: IRB00070087, R01AG042127
Study First Received: October 27, 2013
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
cerebrovascular function

Additional relevant MeSH terms:
Vascular Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Antihypertensive Agents
Hypertension
Cognition Disorders
Cardiovascular Diseases
Mental Disorders
Lisinopril
Candesartan
Candesartan cilexetil
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 28, 2014