Effect of Hydralazine on Alzheimer's Disease

Study aim: 1. Determination and comparison of the effect of 75mg (25mg TDS) hydralazine vs. placebo in patients with mild to moderate Alzheimer's disease. 2. Development of an electronic Case Report Form (CRF) and push notification system to remind patients (and/or caregivers) of drug intake to improve drug intake adherence and reduce follow-up losses. 3. Evaluation of the prognostic accuracy of olfactory tests to predict the changes in cognition and performance of patients with mild to moderate Alzheimer's disease. Design: This is a phase III, triple-blind, parallel double-armed randomized clinical trial with an allocation ratio of 1-1 to the intervention and placebo arms. This trial will be conducted on 424 randomly selected patients using random permuted blocks. Settings and conduct: All patients who are identified as potentially eligible by the supporting neurologists and psychiatrists will be referred to Adineh Clinic to evaluate their cognitive function, assess for inclusion and exclusion criteria and obtain informed consent. The two arms of the study are hydralazine 75mg (25mg three times per day) or hydralazine placebo. A follow-up evaluation will continue for one year after drug administration. The participants, outcome assessors, researchers, and data analyzers will be blinded to the study arms. Participants/Inclusion and exclusion criteria: patients aged 50 and over who are diagnosed with mild to moderate AD will be included in this study; dementia patients with etiologies other than AD (i.e. vascular dementia) will not be included. Intervention groups: The two arms of the study are Hydralazine 75mg (25mg three times per day) or Hydralazine placebo. Main outcome variables: Various cognitive and function tests for patients and caregivers, olfactory tests, biochemistry as well as drug side effects will be assessed regularly over the period of follow-up. Treatment was initiated at 37.5 mg/day (12.5 mg three times daily) and titrated to 75 mg/day (25 mg three times daily) over two weeks. Randomization was stratified by age (under 65 versus 65 and older), sex, and baseline MMSE score (12-18 versus 19-26), using permuted blocks of four generated via Sealed Envelope and integrated into the study eCRF. Independent oversight was provided by a Data Monitoring Committee and a Data and Safety Monitoring Committee, and by the Clinical Trial Centres of Kermanshah and Yazd Universities of Medical Sciences, under the NIMAD ethics committee. Serum hydralazine concentrations were measured at months 6 and 12 to assess adherence. Adherence was supported by an electronic Case Report Form with SMS reminders and participant logbooks. Screening included the Schedule for Affective Disorders and Schizophrenia (SADS) and electrocardiography (ECG).