Clinical trial NCT02471833: Health Evaluation in African Americans Using RAS Therapy
Official title: Health Evaluation in African Americans Using RAS Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alzheimer's Disease
Keywords: hypertension
prevention
family history
inflammation
blood brain barrier
amyloid
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2015-06-15
Enrollment: 61
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: This study will assess if telmisartan, an FDA approved blood pressure medication, may also have beneficial effects on Alzheimer's disease (AD) prevention in African Americans, who are at high risk for Alzheimer's disease. Blood pressure medications known as angiotensin-receptor blockers have been associated with reduced risk of Alzheimer's in Caucasians because they act on the renin-angiotensin system (RAS), a key regulator of blood pressure in the body and the brain. The drugs appear to slow the progression of the disease by affecting flow of blood and the amount of plaque in the brain, but these benefits have not been tested in African Americans. The investigator will evaluate if telmisartan is able to influence the renin-angiotensin system in the brain and produce favorable effects on brain blood flow and enzymes that cause the brain plaques in Alzheimer's disease.The investigator will assess the mechanism by which telmisartan modifies the brain renin angiotensin system, cerebrospinal fluid amyloid-β, cerebral blood flow (CBF) and inflammatory markers in hypertensive African Americans.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Concentration of Angiotensin Converting Enzyme (ACE 1)
timeFrame: Baseline, Month 8
measure: Concentration of Angiotensin Converting Enzyme 2 (ACE 2)
timeFrame: Baseline, Month 8
measure: Cerebrospinal Fluid Amyloid β40
timeFrame: Baseline, Month 8
measure: Levels of Cerebrospinal Fluid Amyloid β42
timeFrame: Baseline, Month 8
measure: Levels of Cerebrospinal Fluid T-tau
timeFrame: Baseline, Month 8
measure: Levels of Cerebrospinal Fluid P-tau
timeFrame: Baseline, Month 8
Secondary outcomes:
measure: Interleukin-6 (IL-6) Frequency
timeFrame: Baseline, Month 8
measure: Interleukin-7 (IL-7) Frequency
timeFrame: Baseline, Month 8
measure: Interleukin-8 (IL-8) Frequency
timeFrame: Baseline, Month 8
measure: Interleukin-9 (IL-9) Frequency
timeFrame: Baseline, Month 8
measure: Interleukin-10 (IL-10) Frequency
timeFrame: Baseline, Month 8
measure: Monocyte Chemoattractant Protein 1 (MCP-1) Frequency
timeFrame: Baseline, Month 8
measure: Macrophage Derived Protein 1 (MDC-1) Frequency
timeFrame: Baseline, Month 8
measure: Transforming Growth Factor Alpha (TGF-α) Frequency
timeFrame: Baseline, Month 8
measure: Tumor Necrosis Factor Alpha (TNF-α) Frequency
timeFrame: Baseline, Month 8
measure: Intercellular Adhesion Molecule 1 (ICAM-1) Frequency
timeFrame: Baseline, Month 8
measure: Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency
timeFrame: Baseline, Month 8
measure: Matrix Metalloproteinase (MMP) Frequency
timeFrame: Baseline, Month 8
measure: Tissue Inhibitor of Metalloproteinase (TIMP) Frequency
timeFrame: Baseline, Month 8
measure: CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ)
timeFrame: Baseline, Month 8
Other outcomes:
measure: Change in Structural Magnetic Resonance Imaging and White Matter Hyperintensities
timeFrame: Baseline, Month 8
measure: Change in Arterial Spin Labeling-Magnetic Resonance Imaging
timeFrame: Baseline, Month 8
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Whitney Whitney, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.