Candesartan's Effects on Alzheimer's Disease And Related Biomarkers
Condition: Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: Placebo; Candesartan
Intervention description: A matched placebo will be given once daily for 12 months.; 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.
Intervention MeSH terms: Candesartan; Candesartan cilexetil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 77.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Alzheimer's disease; hypertension medication; Mild Cognitive impairment; Amyloid Beta

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Mild Cognitive Impairment, defined by:

               -  Subjective memory concern

               -  Abnormal memory function documented using the Logical Memory subscale (Delayed
                  Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the
                  maximum score is 25): [<11 for 16 or more years of education; <9 for 8-15 years
                  of education; <6 for <7 years of education]

               -  Montreal Cognitive Assessment (MoCA) < 26

               -  Clinical Dementia Rating scale /Memory sum Box score=0.5

               -  General functional performance sufficiently preserved (Functional Assessment
                  Questionnaire<9)

          -  Amyloid positivity determined by measuring the amyloid content in the brain. This can
             be determined by either cerebrospinal fluid (CSF) amyloid level or an amyloid scan
             (PIB-PET)

        Exclusion Criteria:

          -  Intolerance to ARBs

          -  Current use of ARBs, angiotensin-converting enzyme inhibitors (ACEIs) (use of
             antihypertensive medications other than ACEI or ARBs for other indications is allowed)

          -  Current diagnosis of hypertension or current use of antihypertensive medication that
             is prescribed specifically for hypertensive therapy

          -  SBP less than 110 or DBP less than 40 mm Hg

          -  Renal disease (Creatinine >2.0 mg/dl), hyperkalemia (K>5.5 meq/dl),
             platelets<50,000/μl, or international normalized ratio (INR)>1.9

          -  Active medical or psychiatric diseases that in the judgment of the investigator would
             affect the safety of the subject or scientific integrity of the study

          -  Uncontrolled congestive heart failure reflected by poor exercise tolerance and
             shortness of breath

          -  History of stroke in the past 3 years

          -  Inability to have MRI (eg metal implants or cardiac pacemaker) with an exception for
             those who cannot have an MRI, if all other parts of the study are obtained
             successfully they may still be enrolled in the study, or cognitive assessment or
             inability to assess amyloid positivity (no lumbar puncture and no amyloid scan)

          -  History of increased intracranial pressure (ICP) or bleeding diathesis (from disease
             states or from use of anticoagulants such as warfarin, heparin and related products,
             rivaroxaban or Xarelto, apixaban or Eliquis, edoxaban or Savaysa, dabigatran or
             Pradaxa)

          -  Women of childbearing potential (non-menopausal)

          -  In those who are unable to demonstrate that they understood the details of the study
             (ie lack of decisional-capacity to consent), a study partner/surrogate who can sign on
             their behalf will be required, otherwise they will be excluded

          -  Current use of Lithium, as candesartan may increase lithium concentration to toxic
             levels