Health Evaluation in African Americans Using RAS Therapy

Phase 1

Completed

• Conditions: Alzheimer's Disease
• Interventions: Drug: Placebo; Drug: Telmisartan 20mg; Drug: Telmisartan 40mg

• Registration Number: NCT02471833
• Lead Sponsor: Emory University

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.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-06-10
• Study First Submitted QC: 2015-06-11
• Study First Posted: 2015-06-15
• Primary Completion: 2022-04-15
• Study Completion: 2022-04-15
• Disposition First Submitted: 2023-04-11
• Disposition First Posted: 2023-04-27
• Status Verified: 2024-04
• Results First Submitted: 2024-04-30
• Results First Submitted QC: 2024-04-30
• Last Update Submitted: 2024-04-30
• Results First Posted: 2024-05-23
• Last Update Posted: 2024-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Telmisartan 20mg	Telmisartan 20mg	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.
Telmisartan 40mg	Telmisartan 40mg	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.

Primary Outcome Measures

Name	Time	Method
Concentration of Angiotensin Converting Enzyme 2 (ACE 2)	Baseline, Month 8	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.
Cerebrospinal Fluid Amyloid β40	Baseline, Month 8	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.
Levels of Cerebrospinal Fluid P-tau	Baseline, Month 8	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.
Levels of Cerebrospinal Fluid T-tau	Baseline, Month 8	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.
Concentration of Angiotensin Converting Enzyme (ACE 1)	Baseline, Month 8	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.
Levels of Cerebrospinal Fluid Amyloid β42	Baseline, Month 8	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.

Secondary Outcome Measures

Name	Time	Method
Transforming Growth Factor Alpha (TGF-α) Frequency	Baseline, Month 8	Transforming growth factor alpha inflammatory markers in CSF were examined.
Intercellular Adhesion Molecule 1 (ICAM-1) Frequency	Baseline, Month 8	Intercellular adhesion molecule 1 inflammatory markers in CSF were examined.
Interleukin-6 (IL-6) Frequency	Baseline, Month 8	The inflammatory marker IL-6 in CSF was examined.
Interleukin-8 (IL-8) Frequency	Baseline, Month 8	The inflammatory marker IL-8 in CSF was examined.
Interleukin-9 (IL-9) Frequency	Baseline, Month 8	The inflammatory marker IL-9 in CSF was examined.
Interleukin-10 (IL-10) Frequency	Baseline, Month 8	The inflammatory marker IL-10 in CSF was examined.
Matrix Metalloproteinase (MMP) Frequency	Baseline, Month 8	Matrix metalloproteinase inflammatory markers will be examined in CSF.
CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ)	Baseline, Month 8	Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ) is a marker of breakdown in the blood brain barrier. Increased levels of sPDGFRβ indicate cognitive dysfunction.
Macrophage Derived Protein 1 (MDC-1) Frequency	Baseline, Month 8	Macrophage derived protein 1 inflammatory markers in CSF were examined.
Tissue Inhibitor of Metalloproteinase (TIMP) Frequency	Baseline, Month 8	Tissue inhibitor of metalloproteinase inflammatory markers will be examined in CSF.
Interleukin-7 (IL-7) Frequency	Baseline, Month 8	The inflammatory marker IL-7 in CSF was examined.
Monocyte Chemoattractant Protein 1 (MCP-1) Frequency	Baseline, Month 8	Monocyte chemoattractant protein 1 inflammatory markers in CSF were examined.
Tumor Necrosis Factor Alpha (TNF-α) Frequency	Baseline, Month 8	Tumor necrosis factor alpha inflammatory markers in CSF were examined.
Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency	Baseline, Month 8	Vascular cell adhesion molecule 1 inflammatory markers in CSF were examined.

Trial Locations

Locations (1)

Emory University; 🇺🇸 Atlanta, Georgia, United States