Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's (SEAIRA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00980785
First received: September 18, 2009
Last updated: July 25, 2012
Last verified: July 2012
  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 4

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

Resource links provided by NLM:


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 ]

Enrollment: 14
Study Start Date: April 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching Placebo
Drug: Placebo
Matching Placebo
Experimental: Active
Ramipril 5mg/day
Drug: Ramipril
Ramipril 5 mg/day
Other Name: Altace

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
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, see Learn About Clinical Studies.

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

Locations
United States, Wisconsin
Wisconisn Alzheimer's Disease Research Center
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00980785     History of Changes
Other Study ID Numbers: H-2009-0036
Study First Received: September 18, 2009
Last Updated: July 25, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
Alzheimer's Disease
Hypertension

Additional relevant MeSH terms:
Alzheimer Disease
Hypertension
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Vascular Diseases
Antihypertensive Agents
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014