A new clinical trial is exploring the potential of hydralazine, a commonly used vasodilator, as a treatment to slow the progression of early-stage Alzheimer's disease (AD). The Effect of Hydralazine on mild to moderate -Stage Alzheimer’s disease (EHSAN) study is a randomized, triple-blind, placebo-controlled trial designed to evaluate the drug's impact on cognitive function over a 52-week period. The trial is being conducted at Adineh Health Clinic (AHC) in Yazd, Iran.
Trial Design and Participants
The EHSAN trial aims to enroll 424 participants aged 50 years or older who have been diagnosed with mild to moderate AD, as evidenced by Mini-Mental State Examination (MMSE) scores between 12 and 26. Participants must also meet the NINCDS-ADRDA criteria for possible or probable AD. The study employs a 1:1 allocation ratio, with participants randomly assigned to receive either 75 mg of hydralazine daily (25 mg three times daily) or a matching placebo. All participants will continue to receive their regular physician-prescribed treatments, such as donepezil, memantine, rivastigmine, or galantamine.
Key inclusion criteria also require participants to have a consistent caregiver who can manage medication, accompany them to appointments, and evaluate their condition. Exclusion criteria include non-Alzheimer's primary dementia, current major depression or substance abuse, uncontrolled systemic illness, and current treatment with hydralazine.
Assessments and Outcome Measures
The primary outcome measure of the EHSAN trial is the Alzheimer's Disease Assessment Scale Version 11.0 (ADAS-cog), a widely used tool for assessing the severity of cognitive and behavioral impairments in AD patients. The ADAS-cog includes tasks such as word recall, object naming, and orientation, with scores ranging from 0 to 70, where higher scores indicate greater impairment.
Secondary outcome measures include:
- The Lawton Instrumental Activities of Daily Living Scale, which measures functional abilities in performing daily activities.
- The Neuropsychiatric Inventory (NPI), which examines psychological and behavioral issues in dementia patients.
- The Caregiver Activity Survey (CAS), which evaluates the amount of time caregivers spend assisting patients with daily activities.
Hydralazine Dosage and Monitoring
Participants in the hydralazine arm will start with a dose of 37.5 mg daily, which will be increased to 75 mg daily after two weeks if well-tolerated. The intervention pills have undergone chemical analysis, and serum levels of hydralazine will be measured in a random sample of 20 patients during the study to ensure adherence. Participants will be closely monitored for adverse events, particularly hypotension, syncopal episodes, falls, and heart failure, given the potential risks associated with hydralazine.
Statistical Analysis and Data Management
The study's primary hypothesis posits that hydralazine will significantly delay AD progression compared to placebo, as measured by the ADAS-cog. The primary endpoint analysis will utilize a repeated measures mixed effects model. Interim monitoring will emphasize adherence to protocol, baseline equality of treatment groups, data retrieval completeness, total patient enrollment, and safety and efficacy of the treatment.
Data collection, coding, and entry will be manually carried out by the research staff, with access to identifying participant information restricted to authorized personnel only. The study's protocol, dataset, and statistical code are available through the corresponding author.
Significance of the Study
Alzheimer's disease is a major public health challenge, with a significant unmet need for effective treatments that can slow disease progression. This trial could provide valuable insights into the potential of hydralazine as a novel therapeutic option for early-stage AD. The results of the EHSAN trial are expected to contribute to the understanding of hydralazine's effects on cognitive function, daily living activities, neuropsychiatric symptoms, and caregiver burden in AD patients.
