HypertensionPhase 2CALIBREXNCT01984164
CAndesartan vs LIsinopril Effects on the BRain
A Phase 2 study testing Candesartan and Lisinopril in people with Hypertension and Mild Cognitive Impairment, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Hypertension, Mild Cognitive Impairment
- What is being tested?
- Candesartan and Lisinopril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2014to 3 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)
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.
Read the 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
- Being tested
- Candesartan, Lisinopril
- Keywords
- Cerebrovascular function
- Medical subject headings
- Hypertension, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CandesartanDrug
Also called Atacand
blinded
LisinoprilDrug
Blinded
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Lisinopril |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 12 months
Secondary outcomes (6)
Memory
To assess episodic memory, the Hopkins Verbal Learning Test-Revised (HVLT-R) will be used. The retention (%) score is calculated by dividing the delayed recall trial by the higher of 3 learning trials. Each trial scores 0 (min) to 12 (max). The HVLT-R retention score is a percentage, and a higher percentage represents a better outcome.
Measured: 12 months
Language
This will be measured using the Boston Naming Test. BNT is a neuropsychological test used to assess visual confrontation naming and language performance in participants with cognitive decline. Its short 15-item version consists of drawings of objects ranging from common objects to less familiar objects. Scale: 0 (min score) to 15 (max score). For this test, a higher score/response represents a better outcome.
Measured: 12 months
Attention Measured Using Digit Span Backward
The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span backwards, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in reverse order (backward span). Backward span is an executive task particularly dependent on working memory. The Digit Span backward is scored for backwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome.
Measured: 12 months
White Matter Lesion Volume
White Matter Lesion volume: high-resolution anatomical images are acquired for the measurement of microvascular disease. WMH volumes will be obtained from Fluid attenuated inversion recovery (FLAIR) imaging sequence and reported as total volume (in mm3). Higher values means greater WMH
Measured: 12 months
Cerebral Perfusion
ASL-MRI: Arterial Spin Labeling (ASL) MRI is non-invasive measure of perfusion that does not require contrast, and allows multiple brain regions mapping of perfusion and reserve. ASL-MRI provides measures of cerebral blood flow (CBF). Higher values indicates higher CBF.
Measured: 12 months
Attention Measured Using Digit Span Forward
This will be measured using Digit Span Forward. The Digit Span test is a subtest of both the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scales (WMS). For the digit span forward, subjects are read a sequence of numbers and asked to repeat the same sequence back to the examiner in the correct order (forward span). Forward span captures attention efficiency and capacity. The Digit Span forward is scored for forwards performance. Scale: 0 (minimum) to 16 (maximum). A higher score represents a better outcome.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2013 (estimated)
- Study start20 Aug 2014
- Primary completion3 Dec 2018
- Study completion3 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Ihab Hajjar, Emory University
- Investigators
- Ihab Hajjar, MD, MS, Principal investigator, Emory Univeristy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01984164
- Sponsor's protocol ID
- IRB00070087
- Other IDs
- R01AG042127
- Acronym
- CALIBREX
- Status last verified
- Feb 2021
- First submitted
- 27 Oct 2013
- Last updated
- 21 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32761160
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)
- ClinicalTrials.gov ID
- NCT01984164
- Acronym / sponsor ID
- CALIBREX / IRB00070087
- Conditions
- Hypertension, Mild Cognitive Impairment
- Keywords
- Cerebrovascular function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 20 Aug 2014 (actual)
- Primary completion
- 3 Dec 2018 (actual)
- Study completion
- 3 Dec 2018 (actual)
- First posted
- 14 Nov 2013 (estimated)
- Results
- Posted 21 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Candesartan | Active comparator | Drug: CandesartanTo 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. |
| Lisinopril | Active comparator | Drug: LisinoprilTo 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. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (11 listed)
- Intolerance to study drugs;
- SBP >200 or DBP >110 mm Hg;
- Renal disease or hyperkalemia
- Active medical or psychiatric problems
- Uncontrolled congestive heart failure;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CandesartanAlso: Atacandblinded | Drug | Candesartan |
| LisinoprilBlinded | Drug | Lisinopril |
Primary outcome
Executive Function
Time frame: 12 months
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.
NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box.
Time frame: 12 months
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)
6 secondary outcomes
Memory
Time frame: 12 months
Language
Time frame: 12 months
Attention Measured Using Digit Span Backward
Time frame: 12 months
White Matter Lesion Volume
Time frame: 12 months
Cerebral Perfusion
Time frame: 12 months
Attention Measured Using Digit Span Forward
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32761160Hajjar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ihab Hajjar, MD, MS principal investigator
Emory Univeristy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Candesartan and Lisinopril in people with Hypertension and Mild Cognitive Impairment, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Executive Function (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01984164, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.