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

NCT ID: NCT02646982

Last Updated: 2022-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2020-08-17

Brief 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.

Detailed Description

This is a double-blind placebo-control randomized clinical trial that compares candesartan to placebo in individuals with mild cognitive impairment (MCI) who also have positive Alzheimer's Disease (AD) biomarkers. The investigators will assess if blocking the effect of Ang II using angiotensin receptor blockers (ARBs) is safe in non hypertensive MCI individuals and whether the use of candesartan will be associated with changes in cerebrospinal fluid disease biomarkers.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Candesartan

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).

Group Type: EXPERIMENTAL

Candesartan

Intervention Type: DRUG

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.

Placebo

Participants will receive a matched placebo once a day orally for 12 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

A matched placebo will be given once daily for 12 months.

Interventions

Placebo

A matched placebo will be given once daily for 12 months.

Intervention Type: DRUG

Candesartan

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 Type: DRUG

Other Intervention Names

Atacand

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Ihab Hajjar

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ihab Hajjar, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Wesley Woods Center

Atlanta, Georgia, United States

Countries

United States

References

Hajjar I, Okafor M, Wan L, Yang Z, Nye JA, Bohsali A, Shaw LM, Levey AI, Lah JJ, Calhoun VD, Moore RH, Goldstein FC. Safety and biomarker effects of candesartan in non-hypertensive adults with prodromal Alzheimer's disease. Brain Commun. 2022 Oct 25;4(6):fcac270. doi: 10.1093/braincomms/fcac270. eCollection 2022.

Reference Type: DERIVED

PMID: 36440097 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01AG049752

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00084574

Identifier Type: -

Identifier Source: org_study_id