NCT01984164

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
176

participants targeted

Target at P50-P75 for phase_2 hypertension

Timeline
Completed

Started Aug 2014

Longer than P75 for phase_2 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 27, 2013

Completed
18 days until next milestone

First Posted

Study publicly available on registry

November 14, 2013

Completed
9 months until next milestone

Study Start

First participant enrolled

August 20, 2014

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 3, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 3, 2018

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

February 21, 2021

Completed
Last Updated

February 21, 2021

Status Verified

February 1, 2021

Enrollment Period

4.3 years

First QC Date

October 27, 2013

Results QC Date

December 14, 2020

Last Update Submit

February 2, 2021

Conditions

HypertensionMild Cognitive Impairment

Keywords

Cerebrovascular function

Outcome Measures

Primary Outcomes (2)

  • Executive Function

    Executive function will be assessed using Trail Making Test (part B-A). Part A was collected to correct for motor speed and visual-perceptual demands on TMT by subtracting completion time for TMT Part A from completion time for Part B (TMT B - A). TMT Part B-A provides a relatively purer measure of executive functioning. It has a timed scale from 0 sec (min) to 300 secs (max). Along this scale, a lower score is better.

    12 months

  • NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box.

    EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" tool box. This test batteryThe battery includes 11 tasks that generate 15 primary variables. Within this set, the EXAMINER includes: working memory, inhibition, set shifting, and fluency. The parts of EXAMINER that were used for this study include: Flanker task (inhibition) which involves responding to a central stimulus while ignoring flanking stimuli that are either compatible or incompatible with the central stimulus; Set-shifting, a measure of mental flexibility; Spatial 1-Back test assesses spatial working memory; Dot Counting test assesses verbal working memory; Verbal Fluency tested using a List Generation test which require the participant to generate words beginning with a specific letter, and category fluency in which the participant generates words from a specified category (e.g., animals, fruits). Higher are reflective of better executive function (-1 to +1)

    12 months

Secondary Outcomes (6)

  • Memory

    12 months

  • Language

    12 months

  • Attention Measured Using Digit Span Backward

    12 months

  • White Matter Lesion Volume

    12 months

  • Cerebral Perfusion

    12 months

  • +1 more secondary outcomes

Study Arms (2)

Candesartan

ACTIVE COMPARATOR

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

Lisinopril

ACTIVE COMPARATOR

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

Interventions

CandesartanDRUG

blinded

Also known as: Atacand
Candesartan
LisinoprilDRUG

Blinded

Lisinopril

Eligibility Criteria

Age55 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age: 55 years or older;
  • Hypertension: SBP≥140 mm Hg or DBP≥ 90 mm or receiving antihypertensive medications.
  • Executive MCI will be defined using these criteria:
  • The Montreal Cognitive Assessment (MoCA) score less than or equal to 26
  • 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.
  • Minimal Functional limitation as reflected by the Functional Assessment Questionnaire (FAQ)≤7

You may not qualify if:

  • Intolerance to study drugs;
  • SBP \>200 or DBP \>110 mm Hg;
  • Renal disease or hyperkalemia
  • Active medical or psychiatric problems
  • Uncontrolled congestive heart failure;
  • History of stroke in the past 3 years;
  • Inability to perform the study procedures
  • Women of childbearing potential
  • diagnosis of dementia
  • 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
  • Current use of Lithium, as most antihypertensive classes may lead to increased lithium toxic levels.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Emory Univeristy

Atlanta, Georgia, 30329, United States

Location

Related Publications (1)

  • 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.

    PMID: 32761160DERIVED

MeSH Terms

Conditions

HypertensionCognitive Dysfunction

Interventions

candesartancandesartan cilexetilLisinopril

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

DipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and Proteins

Limitations and Caveats

A limitation of this study is its 1-year study period. Additional limitations include the relatively small sample size, which limited our power to correct for multiple comparisons.

Results Point of Contact

Title
Dr. Hajjar
Organization
Emory University
ihabhajjar@emory.edu
404-712-2036

Study Officials

  • Ihab Hajjar, MD, MS

    Emory Univeristy

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

October 27, 2013

First Posted

November 14, 2013

Study Start

August 20, 2014

Primary Completion

December 3, 2018

Study Completion

December 3, 2018

Last Updated

February 21, 2021

Results First Posted

February 21, 2021

Record last verified: 2021-02

Locations

US(1)