Clinical trial NCT01984164: CAndesartan vs LIsinopril Effects on the BRain
Official title: CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Mild Cognitive Impairment
Keywords: Cerebrovascular function
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2013-11-14
Enrollment: 176
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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.

Primary outcomes:
measure: Executive Function
timeFrame: 12 months
measure: NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box.
timeFrame: 12 months
Secondary outcomes:
measure: Memory
timeFrame: 12 months
measure: Language
timeFrame: 12 months
measure: Attention Measured Using Digit Span Backward
timeFrame: 12 months
measure: White Matter Lesion Volume
timeFrame: 12 months
measure: Cerebral Perfusion
timeFrame: 12 months
measure: Attention Measured Using Digit Span Forward
timeFrame: 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Univeristy
state: Georgia
Study officials:
affiliation: Emory Univeristy
name: Ihab Hajjar, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.