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Health Evaluation in African Americans Using RAS Therapy (HEART)

This study is currently recruiting participants.
Verified July 2017 by Whitney Wharton, Emory University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02471833
First Posted: June 15, 2015
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Whitney Wharton, Emory University
  Purpose
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.

Condition Intervention Phase
Alzheimer's Disease Drug: Telmisartan 20mg Drug: Telmisartan 40mg Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Health Evaluation in African Americans Using RAS Therapy

Resource links provided by NLM:


Further study details as provided by Whitney Wharton, Emory University:

Primary Outcome Measures:
  • Change in concentration of cerebrospinal fluid angiotensin metabolites [ Time Frame: Baseline, 8 months from baseline ]
    The cerebrospinal fluid renin-angiotensin system (RAS) will be assessed by measuring levels of angiotensin metabolites simultaneously in a single sample of less than 1ml of cerebrospinal fluid (CSF) using RAS-fingerprint™ technology. The RAS-fingerprint™ is a highly selective and sensitive mass spectrometry method. Change is the difference in the levels of angiotensin metabolites from baseline to eight months from baseline.


Secondary Outcome Measures:
  • Change in levels of plasma angiotensinogen [ Time Frame: Baseline, 4 months from baseline ]
    The levels of plasma angiotensinogen will be measured using high-performance liquid chromatography (HPLC). Change is the difference in levels from baseline to 4 months from baseline.

  • Change in levels of plasma angiotensinogen [ Time Frame: 4 months from baseline, 8 months from baseline ]
    The levels of plasma angiotensinogen will be measured using high-performance liquid chromatography (HPLC). Change is the difference in levels from 4 months from baseline to 8 months from baseline.

  • Change in levels of plasma renin [ Time Frame: Baseline, 4 months from baseline ]
    The levels of plasma renin will be measured by radioimmunoassay. Change is the difference in levels from baseline to 4 months from baseline.

  • Change in levels of plasma renin [ Time Frame: 4 months from baseline, 8 months from baseline ]
    The levels of plasma renin will be measured by radioimmunoassay. Change is the difference in levels from 4 months from baseline to 8 months from baseline.

  • Change in levels of plasma angiotensin converting enzyme [ Time Frame: Baseline, 4 months from baseline ]
    The levels of plasma angiotensin converting enzyme will be measured by the automated spectrophotometric method using continuous fluorescent assay. Change is the difference in levels from baseline to 4 months from baseline.

  • Change in levels of plasma angiotensin converting enzyme [ Time Frame: 4 months from baseline, 8 months from baseline ]
    The levels of plasma angiotensin converting enzyme will be measured by the automated spectrophotometric method using continuous fluorescent assay. Change is the difference in levels from 4 months from baseline to 8 months from baseline.

  • Change in levels of plasma aldosterone [ Time Frame: Baseline, 4 months from baseline ]
    The levels of plasma aldosterone will be measured using high-performance liquid chromatography. Change is the difference in levels from baseline to 4 months from baseline.

  • Change in levels of plasma aldosterone [ Time Frame: 4 months from baseline, 8 months from baseline ]
    The levels of plasma aldosterone will be measured using high-performance liquid chromatography. Change is the difference in levels from 4 months from baseline to 8 months from baseline.

  • Change in levels of cerebrospinal fluid amyloid β42 [ Time Frame: Baseline, 8 months from baseline ]
    Levels of amyloid β42 (Aβ42) in the cerebrospinal fluid will be measured using xMAP technology. Decrease in concentrations of amyloid β42 are indicative of a decrease in cognitive function.

  • Change in levels of cerebrospinal fluid T-tau [ Time Frame: Baseline, 8 months from baseline ]
    Levels of T-tau in the cerebrospinal fluid will be measured using xMAP technology. Increase in concentrations of T-tau are indicative of a decrease in cognitive function.

  • Change in levels of cerebrospinal fluid P-tau [ Time Frame: Baseline, 8 months from baseline ]
    Levels of P-tau in the cerebrospinal fluid will be measured using xMAP technology. Increase in concentrations of P-tau are indicative of a decrease in cognitive function.

  • Change in arterial function [ Time Frame: Baseline, 8 months from baseline ]
    Arterial wall stiffness of the brachial artery will be assessed by pulse wave velocity (PWV). Increased pulse wave velocity indicates lower arterial compliance.

  • Flanker Inhibitory Control and Attention Test [ Time Frame: Baseline, 8 months from baseline ]
    The Flanker task measures attention and inhibitory control. The subject are asked to focus on a given stimulus while inhibiting attention to stimuli (arrows) flanking it. Scoring is based on a combination of accuracy and reaction time and a 2-vector scoring method is used. Each of these vectors ranges between 0 and 5, and the computed score ranges from 0-10. Higher scores indicate higher cognitive function.

  • Set-shifting Test [ Time Frame: Baseline, 8 months from baseline ]
    The set-shifting is a measure of mental flexibility and assesses attributes of compound stimuli, and to shift that attention when required. The subject is asked to determine whether the card contains a target stimulus dimension (a color or a number). If the guess is incorrect, the subject will hear an error sound and the card will not flip over and the subject would guess again. In this way, the subject is taught that a specific dimension of the card (either a color or a number) is 'correct'. The total number of errors across five rounds is scored. Lower scores indicate better performance.

  • Spatial 1-Back Test [ Time Frame: Baseline, 8 months from baseline ]
    Subjects are shown a series of white squares that each appear for a period of 1s in 15 possible locations, equidistant from the center of the computer screen. Subjects are instructed to press the left key when the current square matches the same position as the immediately preceding square and to press the right key when it is in a new location. A number (selected randomly from 1-9) appears centrally on the screen 500 ms after each response and is present on the screen for 1000 ms. Subjects are instructed to recite the number out loud as soon as it appears on the screen before proceeding to the next square; this prevents eye fixation on the location to be remembered. The task consists of 30 trials, with 10 matched trials and 20 non-matched trials. The total number of correct responses for each task is tabulated. Lower scores indicate decreased working memory.

  • Montreal Cognitive Assessment [ Time Frame: Baseline, 8 months from baseline ]
    The Montreal Cognitive Assessment test is a one-page 30-point test. Each criteria is allocated a point. The total possible score is 30 points and a score of 26 or above is considered normal. Lower scores indicate cognitive impairment.

  • Mini Mental State Examination (MMSE) [ Time Frame: Baseline, 8 months from baseline ]
    The Mini Mental State Examination is an 11-question measure that tests five areas of cognitive function; orientation, registration, attention and calculation, recall, and language. Points are allocated for each response.The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment.

  • Wechsler Adult Intelligence Scale (WAIS)-Working Memory subtests [ Time Frame: Baseline, 8 months from baseline ]
    The Wechsler Adult Intelligence Scale (WAIS)-Working Memory subtests measure attention, concentration, mental control and reasoning. The subjects will be given tasks which include digit span, arithmetic and letter-number sequencing. Lower scores are indicative of decreased cognitive function.

  • Wechsler Memory Scale-III Faces Test [ Time Frame: Baseline, 8 months from baseline ]
    Subjects will be shown a number of faces and are asked to identify target faces by responding either "yes" or "no" to each face. The subjects are prompted to keep the target faces in mind and are asked to identify the target faces after a timed delay. Lower scores are indicative of decreased cognitive function.

  • Wechsler Memory Scale-Revised Logical Memory Test [ Time Frame: Baseline, 8 months from baseline ]
    The subjects will be asked to provide oral recall of material read to them. The recall scores are recorded. Lower scores indicate lower recall memory.

  • Rey Auditory Verbal Learning Test [ Time Frame: Baseline, 8 months from baseline ]
    Subjects will be presented with a list of 15 unrelated words via audio recording and asked recall as many as he/she can. This process is repeated twice more, and the score is equal to the total number of words recalled across all three trials. Higher scores indicate better immediate recall and better cognitive function.

  • Arterial Spin Labeling-Magnetic Resonance Imaging [ Time Frame: Baseline, 8 months from baseline ]
    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.

  • Structural Magnetic Resonance Imaging and White Matter Hyperintensities [ Time Frame: Baseline, 8 months from baseline ]
    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.


Estimated Enrollment: 66
Study Start Date: April 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telmisartan 20mg
African American subjects with hypertension and at high risk for Alzheimer's disease will be randomly assigned to receive Telmisartan 20mg once a day orally.
Drug: Telmisartan 20mg
Subjects will be given 20 mg of Telmisartan to be taken orally once a day before bedtime. Subjects will be on Telmisartan 20mg for a duration of 8 months.
Other Name: Micardis
Experimental: Telmisartan 40mg
African American subjects with hypertension and at high risk for Alzheimer's disease will be randomly assigned to receive Telmisartan 40mg once a day orally.
Drug: Telmisartan 40mg
Subjects will be given 40 mg of Telmisartan to be taken orally once a day before bedtime. Subjects will be on Telmisartan 40mg for a duration of 8 months.
Other Name: Micardis
Placebo Comparator: Placebo
African American subjects with hypertension and at high risk for Alzheimer's disease will be randomly assigned to receive placebo once a day orally.
Drug: Placebo
Subjects will be given placebo to be taken orally once a day before bedtime. Subjects will be on placebo for a duration of 8 months.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Treated hypertension (systolic blood pressure ≥ 110 mmHg systolic and ≤ 170 mmHg
  2. Parent with Alzheimer's disease
  3. African American

Exclusion Criteria:

  1. Mean resting blood pressure ≥110 and ≤ 170 mmHg systolic
  2. Currently in another investigational drug study
  3. Current use of renin-angiotensin acting medication
  4. Potassium >5.5 meq/dl at baseline
  5. Creatinine >1.99 mg/dl at baseline
  6. History of stroke
  7. Dementia
  8. Baseline Montreal Cognitive Assessment score <27
  9. Contraindication for lumbar puncture or magnetic resonance imaging
  10. Heart failure
  11. Diabetes Types I and II
  12. Pregnant or nursing women
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471833


Contacts
Contact: Whitney Wharton, PhD 404-712-7359 w.wharton@emory.edu
Contact: Whitney Whitney, PhD 404-712-7359 w.wharton@emory.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Whitney Wharton, PhD    404-712-7359    w.wharton@emory.edu   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Whitney Whitney, PhD Emory University
  More Information

Responsible Party: Whitney Wharton, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT02471833     History of Changes
Other Study ID Numbers: IRB00080192
First Submitted: June 10, 2015
First Posted: June 15, 2015
Last Update Posted: August 1, 2017
Last Verified: July 2017

Keywords provided by Whitney Wharton, Emory University:
Hypertension
Prevention
Family History
inflammation
blood brain barrier
amyloid

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Telmisartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action