NCT04842552

Effect of Hydralazine on Alzheimer's Disease

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

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 424 (estimated)
• Sponsor: Shahid Sadoughi University of Medical Sciences and Health Services · Academic / Other
• Sex: All
• Age: 49 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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 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.

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	Hydralazine hydrochloride 25mg tablets	Hydralazine hydrochloride 25mg tablets three time daily for 365 days (one year)
DRUG	Placebo	Placebo

Timeline

• Start date: 2021-08-02
• Primary completion: 2023-06-01
• Completion: 2023-12-20
• First posted: 2021-04-13
• Last updated: 2022-01-06

Locations

1 site across 1 country: Iran

Regulatory

• FDA-regulated drug study