Abstract

Background: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer’s disease pathology and reduce the rate of disease progression. We report a phase II, two arm, double-blind, placebo-controlled, randomised trial (ISRCTN: 93682878; EudraCT: 2012-003641-15) of losartan to test the efficacy of Reducing pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR). Study population: Men and women aged at least 55 years with mild-to-moderate Alzheimer’s disease (AD) Interventions: Randomly allocated 100mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2 week open-label phase and 2 weeks placebo washout to establish drug tolerability. Outcomes: The primary outcome is the rate of whole brain atrophy as a surrogate measure of disease progression. Secondary outcomes include changes to (i) white matter hyperintensity (WMH) volume and cerebral blood flow (CBF) (also surrogate markers of cognitive decline and disease progression); (ii) performance on a standard series of assessments of memory, cognitive function, activities of daily living and quality of life. Assessments: Major assessments (for all outcomes) and relevant safety monitoring of blood pressure and bloods will be at baseline and 12 months. Additional cognitive assessment will also be conducted at 6 months along with safety blood pressure and blood monitoring. Monitoring of blood pressure, bloods and reported side effects will occur during the open-label phase and during the majority of the post-randomisation dispensing visits. Sample Size: 228 participants to provide at least 182 subjects with final assessments to provide 84% power to detect a 25% difference in atrophy rate (therapeutic benefit) change over 12 months at an alpha level of 0.05. Analysis: Intention-to-treat analysis, estimating between-group differences in outcomes derived from appropriate (linear or logistic) multivariable regression models adjusting for minimisation variables.
Original languageEnglish
Pages (from-to)803-814
Number of pages12
JournalJournal of Alzheimer's Disease
Volume61
Issue number2
Early online date6 Dec 2017
DOIs
Publication statusPublished - 19 Dec 2017

Structured keywords

  • CRICBristol
  • BRTC
  • Centre for Surgical Research
  • BTC (Bristol Trials Centre)

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