A Phase 3 interventional study of Hydralazine hydrochloride 25mg tablets and Placebo in Alzheimer Disease, sponsored by Shahid Sadoughi University of Medical Sciences and Health Services. Completed at 1 site in Iran. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-09-09.
Sponsored by Shahid Sadoughi University of Medical Sciences and Health Services · Phase 3, Interventional, and Treatment
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.
Study aim:
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).
3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.
This study's enrollment of 228 is above the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Shahid Sadoughi University of Medical Sciences and Health Services is the lead sponsor of 4 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hydralazine hydrochloride (25mg tablets) every eight hours (TDS)
Drug: Hydralazine hydrochloride 25mg tablets
Placebo tablets (identical in shape to the active comparator) every eight hours (TDS)
Drug: Placebo
Hydralazine hydrochloride 25mg tablets three time daily for 365 days (one year)
Placebo
Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score from Baseline
Change from baseline to Month 12 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score, hydralazine compared with placebo. The ADAS-Cog total score ranges from 0 to 70; higher scores indicate greater cognitive impairment. The primary endpoint is analyzed using a mixed-effects model for repeated measures (MMRM) across assessments at 3, 6, 9, and 12 months.
Time frame: Baseline, and Months 3, 6, 9, and 12
Change in Lawton Instrumental Activities of Daily Living (IADL) Scale Score from Baseline
Changes in the function of patients with Alzheimer's disease in the hydralazine-treated group compared to placebo- treated using Lawton Activity of Daily Living Scale. Scores range from 0 to 8; higher scores indicate greater independence.
Time frame: Baseline, and Months 3, 6, 9, and 12
Change in Neuropsychiatric Inventory (NPI) Score from Baseline
Changes in the behaviour of the patients with Alzheimer's disease in the hydralazine-treated group compared to placebo-treated using Neuropsychiatric Inventory
Time frame: Baseline, and Months 3, 6, 9, and 12
Change in Caregiver Activity Scale Score from Baseline
Changes in caregiver's spent time for the patients in the hydralazine-treated group compare to placebo using Caregiver Activity Scale. Measures caregiver time (hours) over the prior 24 hours across six activities; higher values indicate greater caregiver time.
Time frame: Baseline, and Months 3, 6, 9, and 12
Plan to share: Yes — Individual patient data (IPD) sharing plan will be decided according to the upcoming requests and the ethics committee approval.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Informed consent form will be shared after recruitment started. CSR and SAP will be shared after recruitment phase was concluded. Study Protocol will be shared after publication.
Access criteria: All requests should be forwarded to the study email address and agreed by the investigators' committee subject to the ethics committee approval.
Ran from Aug 2021 to primary completion in Mar 2026, 55 months.
Of 101 phase 3 interventional studies under Alzheimer Disease, half reached primary completion within 47 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 73. This study's 55 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Hydralazine
Shahid Sadoughi University of Medical Sciences and Health Services