PDE5 Inhibitor for Alzheimer's Disease

NCT07172815 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 174242
• Study Type: interventional
• Target: 244
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Keywords

Alzheimers; PDE5 Inhibitors; Blood Brain Barrier Dysfunction

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Neuropsychometric assessments will be collected at screening, baseline, 6 months and 12 months.

Study Arms (2)

Active drug: PDE5 inhibitor

PLACEBO COMPARATOR

Drug: tadalafil

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

tadalafil DRUG

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.

Active drug: PDE5 inhibitor

Placebo DRUG

Matched Placebo will be taken once daily.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Imperial College London: lead

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Central Study Contacts

Paul Edison, MD, MPhil, PhD, FRCP, FRCPI

CONTACT

+44 7785541923; paul.edison@imperial.ac.uk

Hyacinth Henry

CONTACT

hyacinth.henry@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: September 15, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share