Health Evaluation in African Americans Using RAS Therapy

NCT02471833 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB000801921RF1AG051514
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease prevention in African Americans, who are at high risk for Alzheimer's disease.

Conditions

Alzheimer's Disease

Keywords

hypertension; prevention; family history; inflammation; blood brain barrier; amyloid

Outcome Measures

Primary Outcomes (6)

• Concentration of Angiotensin Converting Enzyme (ACE 1)

  The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 1 helps to regulate blood pressure by converting angiotensin I to angiotensin II.

  Baseline, Month 8

• Concentration of Angiotensin Converting Enzyme 2 (ACE 2)

  The cerebrospinal fluid renin-angiotensin system (RAS) was assessed by measuring levels of angiotensin metabolites in a 1 milliliter (mL) sample of cerebrospinal fluid (CSF). ACE 2 regulates levels of circulating angiotensin II. ACE 2 increases during illness and with Alzheimer's disease.

  Baseline, Month 8

• Cerebrospinal Fluid Amyloid β40

  Levels of amyloid β40 (Aβ40) in the cerebrospinal fluid were measured using LUMIPULSE® technology. The relationship between Aβ40 is non-linear with moderate levels showing the highest risk of future cognitive decline in some studies.

  Baseline, Month 8

• Levels of Cerebrospinal Fluid Amyloid β42

  Levels of amyloid β42 (Aβ42) in the cerebrospinal fluid were measured using LUMIPULSE® technology. Decreases in concentrations of amyloid β42 are indicative of a decrease in cognitive function.

  Baseline, Month 8

• Levels of Cerebrospinal Fluid T-tau

  Levels of T-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of T-tau are indicative of a decrease in cognitive function.

  Baseline, Month 8

• Levels of Cerebrospinal Fluid P-tau

  Levels of P-tau in the cerebrospinal fluid were measured using LUMIPULSE® technology. Increases in concentrations of P-tau are indicative of a decrease in cognitive function.

  Baseline, Month 8

Secondary Outcomes (14)

• Interleukin-6 (IL-6) Frequency

  Baseline, Month 8

• Interleukin-7 (IL-7) Frequency

  Baseline, Month 8

• Interleukin-8 (IL-8) Frequency

  Baseline, Month 8

• Interleukin-9 (IL-9) Frequency

  Baseline, Month 8

• Interleukin-10 (IL-10) Frequency

  Baseline, Month 8

Other Outcomes (2)

• Change in Structural Magnetic Resonance Imaging and White Matter Hyperintensities

  Baseline, Month 8

• Change in Arterial Spin Labeling-Magnetic Resonance Imaging

  Baseline, Month 8

Study Arms (3)

Telmisartan 20mg

EXPERIMENTAL

African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 20mg once a day orally.

Drug: Telmisartan 20mg

Telmisartan 40mg

EXPERIMENTAL

African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive telmisartan 40mg once a day orally.

Drug: Telmisartan 40mg

Placebo

PLACEBO COMPARATOR

African American participants with untreated or treated hypertension and at high risk for Alzheimer's disease who are randomly assigned to receive a placebo to match telmisartan once a day orally.

Drug: Placebo

Interventions

Telmisartan 20mg DRUG

Participants will be given 20 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.

Also known as: Micardis

Telmisartan 20mg

Telmisartan 40mg DRUG

Participants will be given 40 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.

Also known as: Micardis

Telmisartan 40mg

Placebo DRUG

Participants will be given placebo to be taken orally once a day before bedtime, for a duration of 8 months.

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mean resting systolic blood pressure ≥ 110 mmHg and ≤ 170 mmHg
• Family history of Alzheimer's disease
• African American

You may not qualify if:

• Currently in another investigational drug study
• Potassium \>5.0 meq/dL at baseline
• Creatinine \>1.99 mg/dL at baseline
• History of stroke or transient ischemic attack (TIA)
• Dementia
• Current use of a RAS acting medication
• Contraindication for lumbar puncture or magnetic resonance imaging
• Heart failure
• Diabetes Types I and II
• Pregnant or nursing women

Sponsors & Collaborators

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

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Wharton W, Goldstein FC, Tansey MG, Brown AL, Tharwani SD, Verble DD, Cintron A, Kehoe PG. Rationale and Design of the Mechanistic Potential of Antihypertensives in Preclinical Alzheimer's (HEART) Trial. J Alzheimers Dis. 2018;61(2):815-824. doi: 10.3233/JAD-161198.

  PMID: 29254080 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Hypertension; Inflammation

Interventions

Telmisartan

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Unanticipated expenses related to the Coronavirus Disease 2019 (COVID-19) pandemic resulted in less funds toward the end of this study impacting the post processing of neuroimaging scans.The researchers are submitting for additional funding for imaging processing and analyses, as well as searching for an expert who is available to perform imaging processing. Results for the magnetic resonance imaging outcomes will be reported as soon as possible.

Results Point of Contact

• Title: Whitney Wharton, PhD
• Organization: Emory University

w.wharton@emory.edu

404-712-7359

Study Officials

• Whitney Whitney, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 15, 2015
• Study Start: April 1, 2015
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: May 23, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)