Shahid Sadoughi University of Medical Sciences and Health Services
Masoud Mirzaei
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.
Alzheimer Disease
Hydralazine hydrochloride 25mg tablets
Placebo
Phase 3
Study aim: Determination and comparison of the effect of 75mg (25mg TDS) hydralazine vs. placebo in patients with mild to moderate Alzheimer's disease. 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. 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 over the age of 49 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.}}
| Study Type : | Interventional |
| Estimated Enrollment : | 424 participants |
| Masking : | Quadruple |
| Masking Description : | Hydralazine hydrochloride was imported directly from a global supplier, packed in 90 tablet bottles with a specific batch number for drug and placebo not revealed to any of the above parties. |
| Primary Purpose : | Treatment |
| Official Title : | The Effect of Hydralazine on the Early Stage of Alzheimer's Disease: A Randomized Clinical Trial |
| Actual Study Start Date : | August 2, 2021 |
| Estimated Primary Completion Date : | June 1, 2023 |
| Estimated Study Completion Date : | December 20, 2023 |
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: Hydralazine hydrochloride 25mg Hydralazine hydrochloride (25mg tablets) every eight hours (TDS) |
Drug: Hydralazine hydrochloride 25mg tablets |
|
Placebo Comparator: Placebo Placebo tablets (identical in shape to the active comparator) every eight hours (TDS) |
Drug: Placebo |
| Ages Eligible for Study: | 49 Years |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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Recruiting
Adineh Health Centre
Yazd, Iran, Islamic Republic of, 8916713151