NCT00980785: SEAIRA

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

Completed Phase 4 Results posted Last updated 25 August 2020

What this trial tests

Phase 4 trial testing Ramipril in Alzheimer's Disease in 14 participants. Completed in 26 July 2011.

Timeline

9 April 2009

Primary endpoint
26 July 2011

26 July 2011

Quick facts

Lead sponsor	University of Wisconsin, Madison
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	prevention
Enrollment	14
Start date	9 April 2009
Primary completion	26 July 2011
Estimated completion	26 July 2011
Sites	1 location across United States

Drugs / interventions tested

• Ramipril (RAMIPRIL) — full drug profile →
• Placebo

Conditions studied

• Alzheimer's Disease — all drugs for Alzheimer's Disease →
• Hypertension — all drugs for Hypertension →

Sponsor

University of Wisconsin, Madison

Who can join

Adults 40 to 65, any sex, with Alzheimer's Disease or Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cerebrospinal Fluid (CSF) Amyloid Beta-42 (Aβ42) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo Primary · 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.

Group	Value	95% CI
Placebo	-22.5	± 78.7
Active	-31.71	± 90.6

Change in CSF Angiotensin Converting Enzyme (ACE) Levels Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo Secondary · 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.

Group	Value	95% CI
Placebo	-0.10	± 0.21
Active	-0.63	± 0.32

Change in Flow-mediated Vasodilation (FMD) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo Secondary · 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.

Group	Value	95% CI
Placebo	-0.70	± 1.56
Active	-0.29	± 1.23

Change in Augmentation Index (%) Between Baseline and Month 4 in Subjects Taking Ramipril vs Subjects on Placebo Secondary · 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.

Group	Value	95% CI
Placebo	1.7	± 8.9
Active	-1.8	± 2.2

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial.
   Wharton W, Stein JH, Korcarz C, Sachs J, et al · · 2012 · cited 60× · PMID 22776970 · DOI 10.3233/jad-2012-120763
2. A review of the mechanisms underlying selected comorbidities in Alzheimer's disease.
   Maciejewska K, Czarnecka K, Szymański P. · · 2021 · cited 45× · PMID 34121170 · DOI 10.1007/s43440-021-00293-5