Alzheimer DiseasePhase 2NCT07172815
PDE5 Inhibitor for Alzheimer's Disease
A Phase 2 study testing tadalafil in people with Alzheimer Disease, run by Imperial College London.
Trial summary
Alzheimer's disease is the most common cause of dementia in the elderly population. The disease is characterised by the presence of abnormal proteins in the brain, primarily β-amyloid (Aβ) and tau. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- tadalafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 244 participants
- Where
- No sites listed yet
- Study dates
- Sep 2025to Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving and capacity to give informed consent.
- An individual who can act as a reliable study partner with regular contact.
- Participants must meet the clinical criteria of MCI or AD.
- Age from 50 years.
- Mini-Mental State Examination (MMSE) score of 22-28.
- Rosen Modified Hachinski Ischemic score ≤4.
- Fluency in English and evidence of adequate premorbid intellectual functioning
- Likely to be able to participate in all scheduled evaluations and complete all required tests.
Who cannot join
- Any contraindications to the use of tadalafil.
- Significant neurological disease other than MCI due to AD that may affect cognition.
- MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease.
- Current presence of a clinically significant major psychiatric disorder.
- Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
- Any previous enrolment in clinical trials within the last 3 months.
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- History of epilepsy, where seizures or treatment could have contributed to cognitive impairment.
- ST Elevation Myocardial infarction within the last 1 year.
- History of cancer within the last 5 years, except localised skin cancer.
- Other clinically significant abnormality on physical, neurological or laboratory examination that could compromise the study or be detrimental to the patient.
- History of alcohol or drug dependence or abuse within the last 2 years.
- Current use of narcotic medications which could affect cognition.
- Patients who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial.
- Women of childbearing potential.
- Any contraindications to MRI scanning, including contraindications for the use of contrast agents, such as renal failure with the estimated glomerular filtration rate of less than 30 ml/minute or known allergy to gadolinium-based contrast agents.
- Hypersensitivity to PDE-5 inhibitors.
- Patients who are taking nitrates (see detailed list of nitrate medications in section 7.5).
- Severe cardiac diseases.
- Patients with unstable angina or angina occurring during exercise or patients with symptomatic coronary artery disease.
- Patients with New York Heart Association Class 2 or greater heart failure in the last 6 months.
- Patients with uncontrolled arrhythmias, hypotension (< 90/50 mmHg), or uncontrolled hypertension.
- Patients with a stroke within the last 6 months.
- Patients with pericardial constriction.
- Patients with life-threatening arrhythmias.
- Patients with severe renal impairment, defined by eGFR <30 mL/min/1.73 m² or the need for dialysis, and severe hepatic Impairment or any evidence of hepatic failure.
- Any other contraindication listed in SmPC.
- Patients who take one or more of the following medications: PDE-5 inhibitors other than tadalafil, any other investigational drugs other than tadalafil, potent inhibitors of CYP3A4 (see detailed list of drugs and consumables in section 7.5), any anti-amyloid or anti-tau therapies, any other investigational therapies for Alzheimer's disease, and any therapy that may affect Alzheimer's disease, as per the judgement of the Investigator.
- [Only applicable for those agreeing to undertake an optional lumbar puncture] Any contraindications of lumbar puncture, including raised intracranial pressure (ICP) with suspected mass effect, skin infections at the puncture site, suspected spinal epidural abscesses, and cellulitis. Individuals with bleeding disorders that may increase the risk of bleeding (e.g. known bleeding diathesis, anticoagulant therapy, thrombocytopenia, abnormal coagulation parameters like prolonged Prothrombin Time (PT), prolonged activated Partial Thromboplastin Time (aPTT), and abnormal International Normalized Ratio (INR) will be excluded from having lumbar puncture.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Hyacinth Henry contact
About this study
Official title: Evaluating the Safety and Efficacy of PDE-5 Inhibitor: Tadalafil as a Treatment for Early Stages of Alzheimer's Disease
Alzheimer's disease is the most common cause of dementia in the elderly population. The disease is characterised by the presence of abnormal proteins in the brain, primarily β-amyloid (Aβ) and tau. Recent evidence suggests that Phosphodiesterase-5 (PDE-5) enzyme inhibitors may hold therapeutic promise in the treatment of early AD. Findings showed that daily low-dose tadalafil (a PDE5 inhibitor that can cross the BBB) administration in patients with erectile dysfunction and MCI increased relative regional cerebral blood flow in the postcentral gyrus, precuneus, and brainstem. However, the long-term effects of tadalafil on AD progression and biomarkers are not known. However, there is limited evidence regarding its safety and efficacy in AD patients. The primary objective of this study is to assess the safety and tolerability of long-term (1 year) tadalafil treatment in patients who are Aβ-positive MCI and early AD based on NIA-AA criteria. Additionally, the secondary objective of this study is to assess the change in cognitive performance from baseline to follow-up, evaluated using neuropsychometric testing, in MCI and AD patients who are undergoing treatment with tadalafil for 1 year.
- Conditions
- Alzheimer Disease
- Being tested
- tadalafil, Placebo
- Keywords
- Alzheimers, PDE5 Inhibitors, Blood Brain Barrier Dysfunction
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tadalafilDrug
Once daily dose of Tadalafil will be commenced at 10 mg for 2 weeks, followed by an increase to 20 mg for another 2 weeks and finally increased to 40 mg.
PlaceboDrug
Matched Placebo will be taken once daily.
| Study group | Role | What they receive |
|---|---|---|
| Active drug: PDE5 inhibitor | Placebo comparator | Not described Receives: Drug: tadalafil |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of long-term (1 year) tadalafil treatment in MCI and early AD patients.
To assess the safety and tolerability of long-term (1 year) tadalafil treatment in MCI and early AD patients using composite outcome measure of the adverse events evaluated from the safety measurements.
This will be assessed by the number of participants using a composite measure generated from abnormal vital signs, abnormal 12-lead ECG readings, abnormal laboratory (blood) tests, abnormal physical exam findings, and abnormal neurological/psychiatric evaluation.
Measured: Data will be collected at screening, baseline, 3-month, 6-month, 9-month and 12-month follow-up.
Secondary outcomes (1)
To assess the change in cognitive performance from baseline to follow-up evaluated using neuropsychometric testing (change in ADAS-Exec) in MCI and AD patients who are undergoing treatment with tadalafil for 1 year.
Change in combined scores on neuropsychometric testing
- ADAS-Exec Z score
Measured: Neuropsychometric assessments will be collected at screening, baseline, 6 months and 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2025
- Study startSep 2025 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 244 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07172815
- Sponsor's protocol ID
- 174242
- Status last verified
- Sep 2025
- First submitted
- 29 Aug 2025
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Safety and Efficacy of PDE-5 Inhibitor: Tadalafil as a Treatment for Early Stages of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07172815
- Acronym / sponsor ID
- 174242
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimers, PDE5 Inhibitors, Blood Brain Barrier Dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 244 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Sep 2025 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 15 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alzheimer's disease is the most common cause of dementia in the elderly population. The disease is characterised by the presence of abnormal proteins in the brain, primarily β-amyloid (Aβ) and tau. Recent evidence suggests that Phosphodiesterase-5 (PDE-5) enzyme inhibitors may hold therapeutic promise in the treatment of early AD. Findings showed that daily low-dose tadalafil (a PDE5 inhibitor that can cross the BBB) administration in patients with erectile dysfunction and MCI increased relative regional cerebral blood flow in the postcentral gyrus, precuneus, and brainstem. However, the long-term effects of tadalafil on AD progression and biomarkers are not known. However, there is limited evidence regarding its safety and efficacy in AD patients. The primary objective of this study is to assess the safety and tolerability of long-term (1 year) tadalafil treatment in patients who are Aβ-positive MCI and early AD based on NIA-AA criteria. Additionally, the secondary objective of this study is to assess the change in cognitive performance from baseline to follow-up, evaluated using neuropsychometric testing, in MCI and AD patients who are undergoing treatment with tadalafil for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active drug: PDE5 inhibitor | Placebo comparator | Drug: tadalafil |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Capable of giving and capacity to give informed consent.
- An individual who can act as a reliable study partner with regular contact.
- Participants must meet the clinical criteria of MCI or AD.
- Age from 50 years.
- Mini-Mental State Examination (MMSE) score of 22-28.
Key exclusion criteria (28 listed)
- Any contraindications to the use of tadalafil.
- Significant neurological disease other than MCI due to AD that may affect cognition.
- MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease.
- Current presence of a clinically significant major psychiatric disorder.
- Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tadalafilOnce daily dose of Tadalafil will be commenced at 10 mg for 2 weeks, followed by an increase to 20 mg for another 2 weeks and finally increased to 40 mg. | Drug | Active drug: PDE5 inhibitor |
| PlaceboMatched Placebo will be taken once daily. | Drug | Placebo |
Primary outcome
To assess the safety and tolerability of long-term (1 year) tadalafil treatment in MCI and early AD patients.
Time frame: Data will be collected at screening, baseline, 3-month, 6-month, 9-month and 12-month follow-up.
To assess the safety and tolerability of long-term (1 year) tadalafil treatment in MCI and early AD patients using composite outcome measure of the adverse events evaluated from the safety measurements. This will be assessed by the number of participants using a composite measure generated from abnormal vital signs, abnormal 12-lead ECG readings, abnormal laboratory (blood) tests, abnormal physical exam findings, and abnormal neurological/psychiatric evaluation.
1 secondary outcome
To assess the change in cognitive performance from baseline to follow-up evaluated using neuropsychometric testing (change in ADAS-Exec) in MCI and AD patients who are undergoing treatment with tadalafil for 1 year.
Time frame: Neuropsychometric assessments will be collected at screening, baseline, 6 months and 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hyacinth Henry contact
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tadalafil in people with Alzheimer Disease, run by Imperial College London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paul Edison, MD, MPhil, PhD, FRCP, FRCPI (+44 7785541923, paul.edison@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability of long-term (1 year) tadalafil treatment in MCI and early AD patients. (time frame: Data will be collected at screening, baseline, 3-month, 6-month, 9-month and 12-month follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.