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Background: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer's disease (AD) pathology and reduce the rate of disease progression.Objective: To conduct a phase II, two arm, double-blind, placebo-controlled, randomized trial of losartan to test the efficacy of Reducing pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR).Methods: Men and women aged at least 55 years with mild-to-moderate AD will be randomly allocated 100 mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2-week open-label phase and 2-week placebo washout to establish drug tolerability. 228 participants will 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. We will use intention-to-treat analysis, estimating between-group differences in outcomes derived from appropriate (linear or logistic) multivariable regression models adjusting for minimization variables.Results: The primary outcome will be rate of whole brain atrophy as a surrogate measure of disease progression. Secondary outcomes will include changes to 1) white matter hyperintensity volume and cerebral blood flow; 2) performance on a standard series of assessments of memory, cognitive function, activities of daily living, and quality of life. 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 self-reported side effects will occur during the open-label phase and during the majority of the post-randomization dispensing visits.Conclusion: This study will identify whether losartan is efficacious in the treatment of AD and whether definitive Phase III trials are warranted. [ABSTRACT FROM AUTHOR]

Obesity is associated with significant morbidity and mortality, which can be attributed to increased risk of a number of medical conditions including, type 11 diabetes mellitus, hypertension and coronary heart disease. The most common cause of premature mortality in the obese population, less well known, are associations between obesity and several cancers including breast, endometrial, prostate and bowel cancer. Obesity predisposes to osteoarthritis, particularly, in the large weight-bearing joints and to respiratory problems including obstructive sleep apnoea. Thus, obesity poses an immense and increasing public health burden.