Health Evaluation in African Americans Using RAS Therapy

Watumiaji waliosajiliwa tu ndio wanaweza kutafsiri nakala

Ingia / Ingia

Kiungo kimehifadhiwa kwenye clipboard

HaliKuajiri

Wadhamini

Emory University

JARIBIO LA KLINIKI: NCT02471833

BioSeek: NCT02471833

Maneno muhimu

Kikemikali

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.

Maelezo

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.

Tarehe

Imethibitishwa Mwisho:	04/30/2019
Iliyowasilishwa Kwanza:	06/09/2015
Uandikishaji uliokadiriwa Uliwasilishwa:	06/10/2015
Iliyotumwa Kwanza:	06/14/2015
Sasisho la Mwisho Liliwasilishwa:	05/30/2019
Sasisho la Mwisho Lilichapishwa:	06/02/2019
Tarehe halisi ya kuanza kwa masomo:	03/31/2015
Tarehe ya Kukamilisha Msingi iliyokadiriwa:	06/29/2020
Tarehe ya Kukamilisha Utafiti:	06/29/2020

Hali au ugonjwa

Alzheimer's Disease

Uingiliaji / matibabu

Drug: Telmisartan 20mg

Drug: Telmisartan 40mg

Drug: Placebo

Awamu

Awamu 1

Vikundi vya Arm

Mkono	Uingiliaji / matibabu
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.
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.
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.

Vigezo vya Kustahiki

Zama zinazostahiki Kujifunza	30 Years Kwa 30 Years
Jinsia Inastahiki Kujifunza	All
Hupokea Wajitolea wa Afya	Ndio
Vigezo	Inclusion Criteria: 1. Treated hypertension (systolic blood pressure ≥ 110 mmHg systolic and ≤ 170 mmHg 2. Parent or biological family member 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

Matokeo

Hatua za Matokeo ya Msingi

1. Change in concentration of cerebrospinal fluid angiotensin metabolites [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.

Hatua za Matokeo ya Sekondari

1. Change in levels of plasma angiotensinogen [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.

2. Change in levels of plasma angiotensinogen [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.

3. Change in levels of plasma renin [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.

4. Change in levels of plasma renin [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.

5. Change in levels of plasma angiotensin converting enzyme [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.

6. Change in levels of plasma angiotensin converting enzyme [4 months from baseline, 8 months from baseline]

7. Change in levels of plasma aldosterone [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.

8. Change in levels of plasma aldosterone [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.

9. Change in levels of cerebrospinal fluid amyloid β42 [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.

10. Change in levels of cerebrospinal fluid T-tau [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.

11. Change in levels of cerebrospinal fluid P-tau [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.

12. Change in arterial function [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.

13. Flanker Inhibitory Control and Attention Test [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.

14. Set-shifting Test [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.

15. Spatial 1-Back Test [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.

16. Montreal Cognitive Assessment [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.

17. Mini Mental State Examination (MMSE) [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.

18. Wechsler Adult Intelligence Scale (WAIS)-Working Memory subtests [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.

19. Wechsler Memory Scale-III Faces Test [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.

20. Wechsler Memory Scale-Revised Logical Memory Test [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.

21. Rey Auditory Verbal Learning Test [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.

22. Arterial Spin Labeling-Magnetic Resonance Imaging [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.

23. Structural Magnetic Resonance Imaging and White Matter Hyperintensities [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.

Health Evaluation in African Americans Using RAS Therapy

Maneno muhimu

inflammation

amyloidosis

angiotensin

amyloid