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The Rationale and Design of the Reducing Pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) Trial

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)803-814
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number2
Early online date6 Dec 2017
DateAccepted/In press - 4 Oct 2017
DateE-pub ahead of print - 6 Dec 2017
DatePublished (current) - 19 Dec 2017


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.

    Structured keywords

  • CRICBristol
  • BRTC
  • Centre for Surgical Research

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via IOS press at Please refer to any applicable terms of use of the publisher

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    Licence: CC BY-NC


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