Candesartan's Effects on Alzheimer's Disease And Related Biomarkers (CEDAR)
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|ClinicalTrials.gov Identifier: NCT02646982|
Recruitment Status : Recruiting
First Posted : January 6, 2016
Last Update Posted : February 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Mild Cognitive Impairment||Drug: Placebo Drug: Candesartan||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Candesartan's Effects on Alzheimer's Disease And Related Biomarkers|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Candesartan will be given orally once a day in a stepwise manner as follows: All participants will be initiated on 8 mg candesartan. The dose will be increased in 2 week increments to 16 mg and 32 mg as long as the systolic blood pressure (SBP) >100 mm Hg, diastolic blood pressure (DBP) >40 mm Hg and participant reports no symptoms of hypotension (dizziness or weakness). The highest achievable dose will be the Maximal Tolerated Dose (MTD) and the participant will receive this dose for the remaining duration of the study (participants will be treated for 1 year).
Candesartan will be started at 8 mg orally, once daily. The dose will be increased in 2 week increments to 16 mg and 32 mg orally, once a day, as long as SBP>100 mm Hg, DBP>40 mm Hg and there are no reported symptoms of hypotension (dizziness or weakness). Candesartan will be given for a total of 12 months.
Other Name: Atacand
Placebo Comparator: Placebo
Participants will receive a matched placebo once a day orally for 12 months.
A matched placebo will be given once daily for 12 months.
- Change in the number hypotensive episodes [ Time Frame: Baseline; 12 months ]Hypotension is defined as blood pressure <100/40 mm Hg. Blood pressure will be measured according to the American Heart Association guidelines with the subject in the sitting position and rested for 5 minutes. An appropriate cuff size (covering 60% of upper arm length and 80% of arm circumference)will be used and correct cuff placement (1-2 inches above the brachial pulse on bare arm) will be ensured.
- Change in the number of subjects with symptoms of hypotension [ Time Frame: Baseline; 12 months ]Subjects will be asked to report any symptoms of hypotension (dizziness, weakness and cough). All subjects will be given a telephone number to reach physician 24-hours per day to report symptoms they experience. The number of subjects reporting symptoms of hypotension will be recorded.
- Changes in the levels of serum creatinine [ Time Frame: Baseline,12 months ]The levels of creatinine will be obtained from blood samples. Increased levels ( >2.5 mg/dl) are indicative of decreased renal function.
- Change in the levels of serum potassium [ Time Frame: Baseline,12 months ]The levels of potassium will be obtained from blood samples. Increased levels of potassium >5.9meq/dl are indicative of decreased renal function.
- Number of subjects discontinuations of candesartan [ Time Frame: At 12 months ]The number of subjects who discontinue candesartan due to any reason will be recorded.
- Changes in cerebrospinal fluid (CSF) phospho-tau181P levels [ Time Frame: Baseline, 12 months ]CSF tau levels will be analyzed from CSF samples obtained via lumbar puncture (LP). Approximately 30-40 ml of CSF will be collected with 24-g Sprotte atraumatic spinal needle. CSF-phospho-tau (p-tau) 181p will be measured using the multiplex xMAP Luminex platform (Luminex Corp, Austin, TX) with Innogenetics (INNO-BIA AlzBio3; Ghent, Belgium; for research use-only reagents) immunoassay kit-based reagents. Higher levels indicate a decrease in cognitive function.
- Changes in cerebrospinal fluid (CSF) amyloid β1-42 levels [ Time Frame: Baseline, 12 months ]CSF amyloid β1-42 levels will be analyzed from CSF samples obtained via lumbar puncture (LP). Approximately 30-40 ml of CSF will be collected with 24-g Sprotte atraumatic spinal needle. Amyloid β1-42 will be measured using the multiplex xMAP Luminex platform (Luminex Corp, Austin, TX) with Innogenetics (INNO-BIA AlzBio3; Ghent, Belgium; for research use-only reagents) immunoassay kit-based reagents. Higher levels indicate a decrease in cognitive function.
- Changes in levels of cerebrospinal fluid cytokines [ Time Frame: Baseline,12 months ]The levels of cytokines in the CSF will be assessed to measure inflammation. Higher levels indicate a decrease in cognitive function.
- Change in arterial stiffness, assessed by Pulse Wave Velocity (PWV) [ Time Frame: Baseline,12 months ]PWV will be measured between the carotid and femoral arteries using the SphygmoCor device to assess aortic stiffness. Pressure waveforms at the carotid and femoral arteries will be acquired using EKG gating. Velocity (distance per time in seconds) will be calculated using the foot-to-foot method and the distance between the sites will be measured manually.
- Changes in aortic stiffness, assessed by Augmentation Index [ Time Frame: Baseline, 12 months ]The Augmentation Index (AI) is a measure of enhanced wave reflection and a measure of aortic stiffness. AI is calculated as augmentation pressure (AG) divided by pulse pressure (PP) ×100 to give a percentage.
- Change in Clinical Dementia Rating (CDR) scores [ Time Frame: Baseline, 12 months ]The CDR rates each of the six general domains involving memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care. A global rating is then generated, ranging from 0=no impairment to 3=severe impairment.
- Change in executive function, assessed by the EXAMINER score and Trail Making Test [ Time Frame: Baseline, 12 months ]The Examiner will be used to measure a participant's attention and inhibitory control. The test requires the participant to focus on a given stimulus while inhibiting attention to stimuli flanking it. Scoring is based on a combination of accuracy and reaction time. Executive function will also be assessed using Trail Making Test (parts B and B-A).
- Changes in memory, assessed by HVL-T [ Time Frame: Baseline, 12 Months ]To assess memory domains we will use the Hopkins Verbal Learning Test (HVLT)
- Change in cerebral vasoreactivity, assessed by MRI [ Time Frame: Baseline, 12 months ]MRI Perfusion Imaging will be used to determine cerebral vasoreactivity. Vasoreactivity (VR)=slope of the regression between cerebral perfusion and end-tidal carbon dioxide (CO2), in ml/100g/min per mm of Hg during normal and hypercapnia.
- Change in white matter hyperintensities (WMH), assessed by structural MRI [ Time Frame: Baseline, 12 months ]High-resolution anatomical images will be acquired using a 3D-Fast Spoiled Gradient Recalled Echo (FSPGR) Sequence. WMH regions will be identified by a 3D T2 Fluid Attenuated Inversion Recovery (FLAIR) Fast Spin Echo sequence.
- Change in functional connectivity, assessed by rs-fMRI [ Time Frame: Baseline, 12 months ]Resting state functional MRI (rs-fMRI) will be used to assess "functional connectivity" between brain regions. The spontaneous, low frequency (<0.1 Hz) fluctuations in the blood oxygenation level-dependent (BOLD) signals will be assessed.
- Global SUVR (PiB and T807) [ Time Frame: Baseline, 12 Months ]In-vivo amyloid imaging will be conducted after intravenous administration of 15±1.5 mCi of [11C] PiB. Images will be analyzed as recently recommended following the ADNI protocol. In-vivo Tau-PET imaging will be conducted using [18F]T807 which has been shown to have selectively high affinity to Tau. T807 PET scans are now available to measure in-vivo Tau content in patients with MCI and AD. Higher levels indicate a decrease in cognitive function.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02646982
|Contact: Ihab Hajjar, MDfirstname.lastname@example.org|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Contact: Ihab Hajjar, MD 404-712-7250 email@example.com|
|Principal Investigator: Ihab Hajjar, MD|
|Wesley Woods Center||Recruiting|
|Atlanta, Georgia, United States, 30329|
|Contact: Ihab Hajjar, MD 404-712-7250 firstname.lastname@example.org|
|Principal Investigator:||Ihab Hajjar, MD||Emory University|