CAndesartan vs LIsinopril Effects on the BRain

NCT ID: NCT01984164

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-20
• Study Completion Date: 2018-12-03

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.

Conditions

Hypertension; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Candesartan

Intervention Type: DRUG

blinded

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.

Group Type: ACTIVE_COMPARATOR

Lisinopril

Intervention Type: DRUG

Blinded

Interventions

Candesartan

blinded

Intervention Type: DRUG

Lisinopril

Blinded

Intervention Type: DRUG

Other Intervention Names

Atacand

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Ihab Hajjar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ihab Hajjar, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Emory Univeristy

Locations

Emory Univeristy

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32761160 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01AG042127

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00070087

Identifier Type: -

Identifier Source: org_study_id