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Completed

NCT Number: NCT02471833

Health Evaluation in African Americans Using RAS Therapy

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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: Micardis

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.

Other names: Micardis

Placebo

Drug

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

Primary outcomes

  1. Concentration of Angiotensin Converting Enzyme (ACE 1)

    Time frame: 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.

  2. Concentration of Angiotensin Converting Enzyme 2 (ACE 2)

    Time frame: 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.

  3. Cerebrospinal Fluid Amyloid β40

    Time frame: 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.

  4. Levels of Cerebrospinal Fluid Amyloid β42

    Time frame: 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.

  5. Levels of Cerebrospinal Fluid T-tau

    Time frame: 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.

  6. Levels of Cerebrospinal Fluid P-tau

    Time frame: 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.

Secondary outcomes

  1. Interleukin-6 (IL-6) Frequency

    Time frame: Baseline, Month 8

    The inflammatory marker IL-6 in CSF was examined.

  2. Interleukin-7 (IL-7) Frequency

    Time frame: Baseline, Month 8

    The inflammatory marker IL-7 in CSF was examined.

  3. Interleukin-8 (IL-8) Frequency

    Time frame: Baseline, Month 8

    The inflammatory marker IL-8 in CSF was examined.

  4. Interleukin-9 (IL-9) Frequency

    Time frame: Baseline, Month 8

    The inflammatory marker IL-9 in CSF was examined.

  5. Interleukin-10 (IL-10) Frequency

    Time frame: Baseline, Month 8

    The inflammatory marker IL-10 in CSF was examined.

  6. Monocyte Chemoattractant Protein 1 (MCP-1) Frequency

    Time frame: Baseline, Month 8

    Monocyte chemoattractant protein 1 inflammatory markers in CSF were examined.

  7. Macrophage Derived Protein 1 (MDC-1) Frequency

    Time frame: Baseline, Month 8

    Macrophage derived protein 1 inflammatory markers in CSF were examined.

  8. Transforming Growth Factor Alpha (TGF-α) Frequency

    Time frame: Baseline, Month 8

    Transforming growth factor alpha inflammatory markers in CSF were examined.

  9. Tumor Necrosis Factor Alpha (TNF-α) Frequency

    Time frame: Baseline, Month 8

    Tumor necrosis factor alpha inflammatory markers in CSF were examined.

  10. Intercellular Adhesion Molecule 1 (ICAM-1) Frequency

    Time frame: Baseline, Month 8

    Intercellular adhesion molecule 1 inflammatory markers in CSF were examined.

  11. Vascular Cell Adhesion Molecule 1 (VCAM-1) Frequency

    Time frame: Baseline, Month 8

    Vascular cell adhesion molecule 1 inflammatory markers in CSF were examined.

  12. Matrix Metalloproteinase (MMP) Frequency

    Time frame: Baseline, Month 8

    Matrix metalloproteinase inflammatory markers will be examined in CSF.

  13. Tissue Inhibitor of Metalloproteinase (TIMP) Frequency

    Time frame: Baseline, Month 8

    Tissue inhibitor of metalloproteinase inflammatory markers will be examined in CSF.

  14. CSF-Soluble Platelet-Derived Growth Factor Receptor Beta (sPDGFRβ)

    Time frame: 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.

Other outcomes

  1. Change in Structural Magnetic Resonance Imaging and White Matter Hyperintensities

    Time frame: Baseline, Month 8

    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.

  2. Change in Arterial Spin Labeling-Magnetic Resonance Imaging

    Time frame: Baseline, Month 8

    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.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Acronym: HEART

Important dates

Study start
2015
Primary completion
2022
Study completion
2022
First posted
Jun 15, 2015
Registry last updated
May 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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