- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00980785
Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's (SEAIRA)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
High blood pressure (BP) in midlife is predictive of Alzheimer's disease (AD) in later life. Similarly, reductions in BP are associated with protection against AD. Treatment with antihypertensive medications, specifically angiotensin converting enzyme inhibitors (ACE-I) such as ramipril, is associated with up to a 55% reduction in the prevalence of AD, suggesting a potentially promising role for ACE-I in the prevention of AD. It is unknown however 1) whether ACE-Is will have the same effect on Cerebrospinal fluid (CSF) Aβ levels in humans as in animal models 2) whether ACE-Is induce changes associated with vascular function (i.e. levels of CSF angiotensin converting enzyme (ACE) and peripheral endothelial function) and 3) whether there are interactions between ACE-I-induced changes in CSF Aβ, CSF ACE and indices of vascular function.
One mechanism by which antihypertensives may protect against AD is via Aβ neuropathology. In order to better understand the mechanisms through which ACE-I may modify CSF Aβ and possibly AD risk, we propose a randomized, double-blind, placebo-controlled pilot clinical trial, enrolling 20 middle-aged (age range 40 - 65 years), mildly hypertensive (between 130 - 160 mmHg mean systolic and between 85 - 100 mmHg mean diastolic) participants, who are adult children of an individual with AD. The main objective of this trial is to examine the effects of the ACE-I, ramipril, on 1) CSF Aβ levels 2) CSF ACE levels and 3) peripheral endothelial function as measured by brachial artery flow-mediated vasodilation (FMD) and aortic augmentation index (AAIx), in middle-aged adults with mildly elevated BP, who are at increased risk of developing AD.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Wisconsin
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Madison, Wisconsin, United States, 53705
- Wisconisn Alzheimer's Disease Research Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Between the ages of 40 and 65
- Mean resting blood pressure between 130-160 systolic and 85-100 diastolic
- Parent with Alzheimer's Disease
Exclusion Criteria:
- Current involvement in another investigational drug trial.
- Potassium > 5.0
- Dementia based on DSMIV criteria
- Mini-Mental State Exam (MMSE) score < 27
- Current blood pressure medication (< 4 months from screening)
- Weight loss medication
- Contraindications for LP
- Know diagnosis or history of hospitalization due to congestive heart failure
- Elevated creatinine (females > 1.3 mg/dL or males > 1.4 mg/dL at baseline)
- Diabetes Type I and II
- Know adverse reaction to an ACE-I or an angiotensin receptor blocker
- Pregnant of nursing women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Matching Placebo
|
Matching Placebo
|
Experimental: Active
Ramipril 5mg/day
|
Ramipril 5 mg/day
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Cerebrospinal Fluid (CSF) Amyloid Beta-42 (Aβ42) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time Frame: Baseline to 4 months
|
CSF Aβ42 levels will be measured from the cerebrospinal fluid taken from subjects on ramipril or placebo at the baseline visit and month 4 and will be measured by Dr. Henrik Zetterberg's laboratory.
|
Baseline to 4 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in CSF Angiotensin Converting Enzyme (ACE) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time Frame: Baseline to 4 months
|
CSF ACE levels will be measured from the cerebrospinal fluid taken from subjects on Ramipril or placebo at the baseline visit and month 4 and will be measured by ARUP® laboratories by spectrophotometric enzymatic assay.
|
Baseline to 4 months
|
Change in Flow-mediated Vasodilation (FMD) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time Frame: Baseline to 4 months
|
FMD is calculated as the ratio of brachial artery diameter after reactive hyperemia to baseline diameter, expressed as percentage change.
FMD for each subject (ramipril v placebo) will be measured at baseline and month 4, observing any differences.
|
Baseline to 4 months
|
Change in Augmentation Index (%) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo
Time Frame: Baseline to 4 months
|
Pulse wave velocity was measured using an AtCor SphymoCor Px tonometry system.
A small pressure transducer was placed on the skin at the point the arterial pulsation of the right common carotid and right radial arteries.
A Millar micromanometer is in the tip of the probe.
Using a generalized transfer function, the distance between these pressure points, and the peripheral arterial waveforms, a central aortic pressure signal is derived, from which aortic augmentation index is determined.
|
Baseline to 4 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Cynthia M Carlsson, MD, MS, University of Wisconsin, Madison
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Cardiovascular Diseases
- Vascular Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Hypertension
- Alzheimer Disease
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Angiotensin-Converting Enzyme Inhibitors
- Ramipril
Other Study ID Numbers
- 2014-1353
- A534255 (Other Identifier: UW Madison)
- SMPH/MEDICINE/GER-AD DEV (Other Identifier: UW Madison)
- H-2009-0036 (Other Identifier: UW Madison IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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