Health Evaluation in African Americans Using RAS Therapy

Alzheimer's Disease Clinical Trial

— HEART  

Official title:

Health Evaluation in African Americans Using RAS Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471833
• Other study ID #: IRB00080192
• Secondary ID: 1RF1AG051514
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: April 15, 2022

Study information

• Verified date: April 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: April 15, 2022
• Est. primary completion date: April 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Telmisartan 20mg
Participants will be given 20 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.
• Telmisartan 40mg
Participants will be given 40 mg of telmisartan to be taken orally once a day before bedtime, for a duration of 8 months.
• Placebo
Participants will be given placebo to be taken orally once a day before bedtime, for a duration of 8 months.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Structural Magnetic Resonance Imaging and White Matter Hyperintensities	High-resolution anatomical images will be acquired using a 3D-Fast Spoiled Gradient Recalled Echo (FSPGR) Sequence. White Matter Hyperintensities (WMH) will be identified by a 3D T2 Fluid Attenuated Inversion Recovery (FLAIR) Fast Spin Echo sequence. The images will be co-registered using a within-subject inter-modal alignment between structural and perfusion images. T1-weighted Spoiled Gradient Recalled (SPGR) images will be used to identify cerebrospinal fluid and white and gray matter. Increased volumes of white matter hyperintensities indicate impaired cognitive function.	Baseline, Month 8
Other	Change in Arterial Spin Labeling-Magnetic Resonance Imaging	Echoplanar T1 mapping scans will be used for image registration and a scout image of the head will be obtained in order to choose the appropriate location for spin labeling and flow imaging. Arterial Spin Labeling images will be acquired using a custom 3D stack of interleaved spirals fast spin echo sequences and will be averaged in order to improve the signal-to-noise ratio. Images will be interpolated and smoothed in a panel by using a 0.5-pixel, full-width, half-maximum Gaussian kernel. Regional perfusion will be quantified in each hemisphere and maps of cerebral vasoreactivity will be obtained by co-registration of perfusion and anatomical images.	Baseline, Month 8
Primary	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
Primary	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
Primary	Cerebrospinal Fluid Amyloid ß40	Levels of amyloid ß40 (Aß40) in the cerebrospinal fluid were measured using LUMIPULSE® technology. The relationship between Aß40 is non-linear with moderate levels showing the highest risk of future cognitive decline in some studies.	Baseline, Month 8
Primary	Levels of Cerebrospinal Fluid Amyloid ß42	Levels of amyloid ß42 (Aß42) in the cerebrospinal fluid were measured using LUMIPULSE® technology. Decreases in concentrations of amyloid ß42 are indicative of a decrease in cognitive function.	Baseline, Month 8
Primary	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
Primary	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	Interleukin-6 (IL-6) Frequency	The inflammatory marker IL-6 in CSF was examined.	Baseline, Month 8
Secondary	Interleukin-7 (IL-7) Frequency	The inflammatory marker IL-7 in CSF was examined.	Baseline, Month 8
Secondary	Interleukin-8 (IL-8) Frequency	The inflammatory marker IL-8 in CSF was examined.	Baseline, Month 8
Secondary	Interleukin-9 (IL-9) Frequency	The inflammatory marker IL-9 in CSF was examined.	Baseline, Month 8
Secondary	Interleukin-10 (IL-10) Frequency	The inflammatory marker IL-10 in CSF was examined.	Baseline, Month 8
Secondary	Monocyte Chemoattractant Protein 1 (MCP-1) Frequency	Monocyte chemoattractant protein 1 inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Macrophage Derived Protein 1 (MDC-1) Frequency	Macrophage derived protein 1 inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Transforming Growth Factor Alpha (TGF-a) Frequency	Transforming growth factor alpha inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Tumor Necrosis Factor Alpha (TNF-a) Frequency	Tumor necrosis factor alpha inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Intercellular Adhesion Molecule 1 (ICAM-1) Frequency	Intercellular adhesion molecule 1 inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency	Vascular cell adhesion molecule 1 inflammatory markers in CSF were examined.	Baseline, Month 8
Secondary	Matrix Metalloproteinase (MMP) Frequency	Matrix metalloproteinase inflammatory markers will be examined in CSF.	Baseline, Month 8
Secondary	Tissue Inhibitor of Metalloproteinase (TIMP) Frequency	Tissue inhibitor of metalloproteinase inflammatory markers will be examined in CSF.	Baseline, Month 8
Secondary	CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRß)	Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRß) is a marker of breakdown in the blood brain barrier. Increased levels of sPDGFRß indicate cognitive dysfunction.	Baseline, Month 8