The Rationale and Design of the Reducing Pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) Trial
| Autor: | Yoav Ben-Shlomo, Beth Howden, Jeremy Horwood, Hannah Baber, Ian B. Malone, Athene Lane, Peter S Blair, Lucy E Selman, Ian B. Wilkinson, Clare Clement, Elizabeth Coulthard, Patrick G. Kehoe, Anthony Peter Passmore, Nick C. Fox, David L. Thomas |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology CRICBristol law.invention Renin-Angiotensin System 0302 clinical medicine Quality of life Randomized controlled trial law Activities of Daily Living Medicine Randomized Controlled Trials as Topic General Neuroscience Brain General Medicine Magnetic Resonance Imaging Psychiatry and Mental health Clinical Psychology Losartan Tolerability Centre for Surgical Research Disease Progression Regression Analysis Female BRTC Alzheimer's disease medicine.drug medicine.medical_specialty Placebo BTC (Bristol Trials Centre) 03 medical and health sciences Clinical Trials Phase II as Topic Double-Blind Method Alzheimer Disease Humans Antihypertensive Agents business.industry medicine.disease Blood Pressure Monitors Clinical trial 030104 developmental biology Blood pressure Multivariate Analysis Quality of Life Atrophy Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Kehoe, P, Ben-Shlomo, Y, Howden, B, Lane, J A, Coulthard, L, Blair, P, Horwood, J, Selman, L & Clement, C 2017, ' The Rationale and Design of the Reducing Pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) Trial ', Journal of Alzheimer's Disease, vol. 61, no. 2, pp. 803-814 . https://doi.org/10.3233/JAD-170101 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-170101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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