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NCT02646982: CEDAR

Candesartan's Effects on Alzheimer's Disease And Related Biomarkers

Completed Phase 2 Results posted Last updated 1 December 2022
What this trial tests

Phase 2 trial testing Placebo in Mild Cognitive Impairment in 77 participants. Completed in 17 August 2020.

Timeline
30 June 2016
Primary endpoint
17 August 2020
17 August 2020

Quick facts

Lead sponsorEmory University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment77
Start date30 June 2016
Primary completion17 August 2020
Estimated completion17 August 2020
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Emory University

Who can join

50 and older, any sex, with Mild Cognitive Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a Hypotensive Episode Primary · Up to Month 12

Hypotension is defined as blood pressure \<100/40 mm Hg. Blood pressure was 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) was used and correct cuff placement (1-2 inches above the brachial pulse on bare arm) was ensured.

GroupValue95% CI
Candesartan16
Placebo4
Number of Participants With Symptoms of Hypotension Primary · Up to Month 12

Participants were asked to report any symptoms of hypotension (dizziness, weakness, fatigue and lightheadedness). All participants were given a telephone number to reach physician 24-hours per day to report symptoms they experience. The number of participants reporting symptoms of hypotension is reported here.

GroupValue95% CI
Candesartan7
Placebo10
Number of Participants With Hypotensive Episodes and Symptoms Primary · Up to Month 12

The number of participants with reported episodes hypotension as well as symptoms of hypotension.

GroupValue95% CI
Candesartan4
Placebo1
Number of Participants With Elevated Serum Creatinine Primary · Up to Month 12

The levels of creatinine were obtained from blood samples. Elevated serum creatinine is defined as levels \>2.5 milligram per deciliter (mg/dL). Elevated serum creatinine is indicative of decreased renal function.

GroupValue95% CI
Candesartan0
Placebo0
Number of Participants With Hyperkalemia Primary · Up to Month 12

The levels of potassium were obtained from blood samples. Hyperkalemia is defined as potassium levels \>5.9 milliequivalent per deciliter (meq/dL). Hyperkalemia is an indication of kidney dysfunction.

GroupValue95% CI
Candesartan0
Placebo1
Number of Participants Discontinuing Study Medication Primary · Up to Month 12

The number of participants who discontinued the study medication is presented here.

GroupValue95% CI
Candesartan0
Placebo1
Cerebrospinal Fluid (CSF) Total Tau Levels Secondary · Baseline, Month 12

CSF total tau (t-tau) levels were analyzed from CSF samples obtained via lumbar puncture. Normal values for t-tau are \< 450 pg/ml. Elevated levels of t-tau indicate worsening disease.

Baseline Total Tau
GroupValue95% CI
Candesartan638.31± 53.61
Placebo529.04± 53.50
Month 12 Total Tau
GroupValue95% CI
Candesartan571.96± 52.89
Placebo441.25± 53.02
Cerebrospinal Fluid (CSF) of Tau Phosphorylated at Threonine 181 (p-tau181) Levels Secondary · Baseline, Month 12

CSF levels of p-tau181 were analyzed from CSF samples obtained via lumbar puncture. P-tau181 is a biomarker that is elevated in persons with Alzheimer's disease. Higher values indicate worsening disease.

Baseline p-tau
GroupValue95% CI
Candesartan100.29± 9.09
Placebo81.58± 9.07
Month 12 p-tau
GroupValue95% CI
Candesartan88.52± 8.58
Placebo68.49± 8.59
Cerebrospinal Fluid (CSF) Amyloid Aβ42 Levels Secondary · Baseline, Month 12

CSF Aβ42 levels were analyzed from CSF samples obtained via lumbar puncture. Aβ42 is a biomarker for Alzheimer's disease and lower values indicate worsening disease and an increased accumulation of amyloid in the brain.

Baseline Aβ42
GroupValue95% CI
Candesartan554.80± 34.09
Placebo523.03± 33.98
Month 12 Aβ42
GroupValue95% CI
Candesartan557.60± 27.32
Placebo476.32± 27.43
Cerebrospinal Fluid (CSF) Amyloid Aβ40 Levels Secondary · Baseline, Month 12

CSF Aβ40 levels were analyzed from CSF samples obtained via lumbar puncture. Lower values indicate worsening disease and an increased brain accumulation of amyloid.

Baseline Aβ40
GroupValue95% CI
Candesartan11624.00± 625.86
Placebo10802.00± 623.82
Month 12 Aβ40
GroupValue95% CI
Candesartan11769.00± 571.54
Placebo9735.00± 573.74
Cerebrospinal Fluid (CSF) Amyloid Aβ42/Aβ40 Levels Secondary · Baseline, Month 12

CSF Aβ42/Aβ40 levels were analyzed from CSF samples obtained via lumbar puncture. A lower ratio indicates worsening disease.

Baseline Aβ42/Aβ40 ratio
GroupValue95% CI
Candesartan0.049± 0.003
Placebo0.052± 0.003
Month 12 Aβ42/Aβ40 ratio
GroupValue95% CI
Candesartan0.050± 0.003
Placebo0.051± 0.003
Pulse Wave Velocity (PWV) Secondary · Baseline, Month 12

Arterial stiffness was assessed by Pulse Wave Velocity (PWV). PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). Lower values indicate a preferable measurement of arterial stiffness.

Baseline
GroupValue95% CI
Candesartan7.817.12 – 8.51
Placebo8.738.05 – 9.40
Month 12
GroupValue95% CI
Candesartan7.717.03 – 8.40
Placebo8.147.47 – 8.81

Adverse events — posted to ClinicalTrials.gov

Time frame: Information on adverse events was collected for the duration of each participant's study enrollment, from the time that individuals gave consent to participate through their final study visit (up to 12 months).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Candesartan
Serious: 0/38 (0%)
Deaths: 0/38
Placebo
Serious: 0/39 (0%)
Deaths: 0/39
Other adverse events (12 terms — click to expand)

ReactionSystemCandesartanPlacebo
DizzinessGeneral disorders
HeadacheGeneral disorders
Fatigue, tiredness, weaknessGeneral disorders
Back painMusculoskeletal and connective tissue disorders
LightheadednessGeneral disorders
RashSkin and subcutaneous tissue disorders
FallInjury, poisoning and procedural complications
Pain at back of headGeneral disorders
Panic attackPsychiatric disorders
Vasovagal syncopeGeneral disorders
Joint painMusculoskeletal and connective tissue disorders
Runny noseGeneral disorders

Data from ClinicalTrials.gov NCT02646982 adverse events section.

Sponsor's own description

This study is intended to investigate the safety of candesartan, a blood pressure medication, in non-hypertensive individuals who have mild cognitive impairment (MCI) due to Alzheimer's disease and its effect on disease biomarkers.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current and Future Treatments in Alzheimer Disease: An Update.
    Yiannopoulou KG, Papageorgiou SG. · · 2020 · cited 553× · PMID 32165850 · DOI 10.1177/1179573520907397
  2. Alzheimer's disease drug development pipeline: 2019.
    Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2019 · cited 485× · PMID 31334330 · DOI 10.1016/j.trci.2019.05.008
  3. Alzheimer's disease drug development pipeline: 2018.
    Cummings J, Lee G, Ritter A, Zhong K. · · 2018 · cited 402× · PMID 29955663 · DOI 10.1016/j.trci.2018.03.009
  4. Alzheimer's disease drug development pipeline: 2020.
    Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2020 · cited 350× · PMID 32695874 · DOI 10.1002/trc2.12050
  5. Alzheimer's disease drug development pipeline: 2017.
    Cummings J, Lee G, Mortsdorf T, Ritter A, et al · · 2017 · cited 258× · PMID 29067343 · DOI 10.1016/j.trci.2017.05.002
  6. Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer's disease.
    Dhapola R, Hota SS, Sarma P, Bhattacharyya A, et al · · 2021 · cited 254× · PMID 34813026 · DOI 10.1007/s10787-021-00889-6
  7. The Coming of Age of the Angiotensin Hypothesis in Alzheimer's Disease: Progress Toward Disease Prevention and Treatment?
    Kehoe PG. · · 2018 · cited 101× · PMID 29562545 · DOI 10.3233/jad-171119
  8. Cognitive Impairment in Heart Failure: Landscape, Challenges, and Future Directions.
    Yang M, Sun D, Wang Y, Yan M, et al · · 2021 · cited 48× · PMID 35198608 · DOI 10.3389/fcvm.2021.831734

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Other trials of Candesartan

Trials testing the same drug.

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Other Emory University trials

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