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COMPLETED

NCT04842552

PHASE3

Effect of Hydralazine on Alzheimer's Disease

Sponsor: Shahid Sadoughi University of Medical Sciences and Health Services

View on ClinicalTrials.gov

Summary

It has been recently discovered that the FDA-approved drug, hydralazine, has anti-neurodegenerative efficacy based on three intriguing observations. hydralazine; 1) activates the Nrf2 pathway that controls more than 200 antioxidant proteins, 2) rejuvenates mitochondria and increases their respiration capacity and adenosine triphosphate production, 3) activates autophagy which has pathophysiological roles such as intracellular aggregate clearance. There is an emerging agreement that autophagy-lysosome defects occur early in the pathogenesis of Alzheimer's disease (AD). Nrf2 is another pathway known to be impaired in the hippocampus of AD patients who need antioxidant protection the most. Rejuvenation of mitochondria is crucial for fighting AD, as neuronal cells need more energy to afford activation of pathways such as autophagy and Nrf2. The prime objective of this application is to conduct a randomized clinical trial to assess the efficacy of hydralazine in early-stage AD patients who take one of the acetylcholinesterase inhibitor (AChEI) donepezil, rivastigmine, or galantamine.

Official title: The Effect of Hydralazine on the Early Stage of Alzheimer's Disease: A Randomized Clinical Trial

Key Details

Gender

All

Age Range

50 Years - Any

Study Type

INTERVENTIONAL

Enrollment

228

Start Date

2021-08-02

Completion Date

2026-03-05

Last Updated

2026-08-27

Healthy Volunteers

Conditions

Alzheimer Disease

Interventions

DRUG

Hydralazine hydrochloride 25mg tablets

Hydralazine hydrochloride 25mg tablets three time daily for 365 days (one year)

DRUG

Placebo

Inclusion Criteria: * Diagnoses of Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. * Presence of a caregiver (friend or relative) who can assume responsibility for medication administrations, accompany the patient to all visits, and rate patient's condition. * Written informed consent form from both the patient (or surrogate) and caregiver. * A Mini-Mental State Examination score between 12 and 26 inclusive. * Prescription of donepezil (5-10mg/d), memantine (5-21mg/d), rivastigmine (3-6mg/d), galantamine or galantamine ER (8-16mg/d) for a minimum of 4 weeks prior to randomization. * Agreement not to take hydralazine. * Age 50 and over. Exclusion Criteria: * Non-Alzheimer primary dementia diagnosis (e.g., vascular dementia, Lewy body dementia, frontotemporal dementia, vitamin B-12 deficiency, hypothyroidism). * Diagnosis of any of the following conditions; major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by Diagnostic and Statistical Manual (DSM)-5. * Diagnosis of systemic illnesses that would interfere with participation in the study or decrease the life expectancy to less than one year. * Currently being treated with hydralazine or a history of intolerance to oral therapy with hydralazine * Any intravenous treatment for heart failure, except IV furosemide (e.g. IV inotropes, pressors, nitrates or nesiritide) at the time of screening. * Systolic blood pressure \<100 mmHg, reversible etiology of acute heart failure such as myocarditis, acute myocardial infarction-over the past 4 weeks, arrhythmia and existence of pacing device (Acute myocardial infarction is defined as symptoms and major electrocardiogram (ECG) changes (i.e., ST segment elevations), and arrhythmia includes unstable heart rates above 120/min or below 50/min). * Existence of severe congenital heart disease (such as uncorrected tetralogy of fallot or transposition of the aorta) and severe aortic or mitral stenosis or severe rheumatic mitral regurgitation. * Concurrent use of phosphodiesterase type 5 (PDE5) inhibitors (e.g. Viagra, Etc.) * Cardiac revascularization within the last 3 months or likelihood of requiring coronary revascularization within the study period. eGFR (Glomerular Filtration Rate) \< 15ml/min/1.73m2, or on regular dialysis, or planned dialysis within the study period.

Locations (1)

Adineh Health Centre

Yazd, Yazd Province, Iran