Studying the Effects of Antihypertensives on Individuals at Risk for Alzheimer's
Condition: Alzheimer's Disease; Hypertension
MeSH terms: Alzheimer Disease; Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): Ramipril; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ramipril 5 mg/day; Matching Placebo
Other intervention name(s): Altace
Intervention MeSH terms: Ramipril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Alzheimer's Disease; Hypertension