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

NCT02646982 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00084574R01AG049752
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 2

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.

Conditions

Mild Cognitive Impairment

Keywords

Alzheimer's disease; hypertension medication; Mild Cognitive impairment; Amyloid Beta

Outcome Measures

Primary Outcomes (6)

• Number of Participants With a Hypotensive Episode

  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.

  Up to Month 12

• Number of Participants With Symptoms of Hypotension

  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.

  Up to Month 12

• Number of Participants With Hypotensive Episodes and Symptoms

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

  Up to Month 12

• Number of Participants With Elevated Serum Creatinine

  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.

  Up to Month 12

• Number of Participants With Hyperkalemia

  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.

  Up to Month 12

• Number of Participants Discontinuing Study Medication

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

  Up to Month 12

Secondary Outcomes (16)

• Cerebrospinal Fluid (CSF) Total Tau Levels

  Baseline, Month 12

• Cerebrospinal Fluid (CSF) of Tau Phosphorylated at Threonine 181 (p-tau181) Levels

  Baseline, Month 12

• Cerebrospinal Fluid (CSF) Amyloid Aβ42 Levels

  Baseline, Month 12

• Cerebrospinal Fluid (CSF) Amyloid Aβ40 Levels

  Baseline, Month 12

• Cerebrospinal Fluid (CSF) Amyloid Aβ42/Aβ40 Levels

  Baseline, Month 12

Study Arms (2)

Candesartan

EXPERIMENTAL

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).

Drug: Candesartan

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

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

Placebo

Candesartan 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.

Also known as: Atacand

Candesartan

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

Wesley Woods Center

Atlanta, Georgia, 30329, United States

Location

Related Publications (1)

• 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.

  PMID: 36440097 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Plaque, Amyloid

Interventions

candesartan; candesartan cilexetil

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Ihab Hajjar, MD
• Organization: University of Texas Southwestern

ihabhajjar@emory.edu

214-645-9533

Study Officials

• Ihab Hajjar, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 6, 2016
• Study Start: June 30, 2016
• Primary Completion: August 17, 2020
• Study Completion: August 17, 2020
• Last Updated: December 1, 2022
• Results First Posted: September 29, 2022

Record last verified: 2022-11

Locations

US (2)