Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's - Full Text View

Sponsor:	University of Wisconsin, Madison
Information provided by:	University of Wisconsin, Madison
ClinicalTrials.gov Identifier:	NCT00980785

Purpose

Angiotensin converting enzyme inhibitors (ACE-I) are a group of blood pressure-lowering medicines. Some studies suggest that ACE-I, such as ramipril, may help prevent Alzheimer's disease (AD). The purpose of the research is to see how ramipril affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal cord. High amounts of beta-amyloid may be associated with a greater risk of getting Alzheimer's disease. This study will see if ramipril can lower the amount of beta-amyloid in the spinal fluid. This study will also see if ramipril affects blood vessel function and memory and thinking. The investigators hope that future studies will show whether ramipril might prevent memory loss and decrease the chance of developing Alzheimer's disease.

Condition	Intervention	Phase
Alzheimer's Disease Hypertension	Drug: Ramipril Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study
Official Title:	Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Blood Pressure Medicines High Blood Pressure

Drug Information available for: Ramipril

U.S. FDA Resources

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:

To determine the effects of 4 months of ramipril therapy on CSF Aβ levels in mildly hypertensive, non-demented adult children of persons with AD when compared to subjects taking placebo. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
To evaluate the effects of 4 months of ramipril on CSF ACE levels in mildly hypertensive, non-demented adult children of persons with AD when compared to subjects taking placebo. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
To determine the effects of 4 months of ramipril therapy on the cardiovascular outcome variables of brachial reactivity and aortic augmentation index in non-demented adult children of persons with AD when compared to subjects taking placebo. [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	April 2009
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo: Placebo Comparator Matching Placebo	Drug: Placebo Matching Placebo
Active: Experimental Ramipril 5mg/day	Drug: Ramipril Ramipril 5 mg/day

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 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.

Eligibility

Ages Eligible for Study:	40 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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
MMSE < 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00980785

Contacts

Contact: Jane F Sachs, BA	(608) 256-1901 ext 11503	jfsachs@medicine.wisc.edu
Contact: Whitney L Wharton, PhD	(608) 256-1901 ext 11516	wlwharto@medicine.wisc.edu

Locations

United States, Wisconsin
Wisconisn Alzheimer's Disease Research Center	Recruiting
Madison, Wisconsin, United States, 53705
Contact: Jane F Sachs, BA 608-256-1901 ext 11503 jfsachs@medicine.wisc.edu
Principal Investigator: Whitney L Wharton, PhD

Sponsors and Collaborators

University of Wisconsin, Madison

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Wisconsin Alzheimer's Disease Research Center ( Whitney Wharton, PhD - Research Scientist )
Study ID Numbers:	H-2009-0036
Study First Received:	September 18, 2009
Last Updated:	September 18, 2009
ClinicalTrials.gov Identifier:	NCT00980785 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:

Alzheimer's Disease
Hypertension

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Alzheimer Disease
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Brain Diseases
Neurodegenerative Diseases
Antihypertensive Agents
Pharmacologic Actions

Ramipril
Protease Inhibitors
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Diseases
Dementia
Tauopathies
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010