Fasudil treatment for early Alzheimer's disease

A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease (FEAD)

This study is testing if fasudil can help improve thinking and memory skills in people with early Alzheimer's disease compared to a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 50 Years to 100 Years
• Sex: All
• Sponsor: Helse Stavanger HF (Government)
• Locations: 6 sites (Tromsø, Nordland and 5 other locations)
• Trial ID: NCT06362707 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial investigates the efficacy of fasudil, a ROCK-inhibitor, in improving cognitive functions in individuals with early Alzheimer's disease. The study is designed as a randomized, placebo-controlled, double-blind trial involving up to 200 participants who will receive either fasudil or a placebo over a 12-month period. Participants will undergo cognitive assessments, FDG-PET scans, and biomarker analyses to evaluate the drug's impact on working memory and other cognitive functions. The treatment will begin with a titration period followed by a maintenance dose, with regular monitoring for safety and efficacy.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 and older with early Alzheimer's disease, specifically those with mild cognitive impairment or mild dementia and validated biomarker changes.

Not a fit: Patients with advanced Alzheimer's disease or those who do not meet the specific biomarker criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to significant improvements in cognitive function for patients with early Alzheimer's disease.

How similar studies have performed: While fasudil has shown promise in animal models, this approach is relatively novel in the context of Alzheimer's disease treatment.

Eligibility criteria

Inclusion Criteria:

* Early AD, eg Stage 3 MCI or Stage 4 (mild AD dementia), as recently defined by the FDA (2018; Figure 2)
* A significant change on a validated AD amyloid or tau biomarker (as determined either by visual reading of amyloid PET scans using any of the approved ligands, or CSF Aβ 1-42 levels or blood p-tau 217 cut-offs as determined by the clinical research laboratory)
* A CDR Global rating of 0.5 or 1.0 (Morris 1993) and have an MRI scan within the past two years that has no findings inconsistent with AD
* Capacity to give informed consent based on the clinical judgement of an experienced clinician
* The participant needs to have a reliable study partner with regular contact (a combination of face-to-face visits and telephone contact is acceptable) who has sufficient interaction with the participant to provide meaningful input into rating scales
* Age from 50 years
* Fluency in Norwegian and evidence of adequate premorbid intellectual functioning
* Capable of participating in all scheduled evaluations and complete all required tests
* Female participants must be of non-childbearing potential or have a negative serum pregnancy test within 14 days of baseline assessments and agree to the use of effective birth control throughout their participation in the study

Exclusion Criteria:

* Significant cerebrovascular disease, as indicated by clinical history, neurological examination, or on MRI (including cortical infarction or deep white matter or periventricular white matter hyperintensities with a Fazekas scale score of 3 (Fazekas et al 1987).
* A history of cerebrovascular bleeding or severe bleeding of the digestive tract, lungs, nose or skin
* Severe renal impairment (GFR \<30) or serum creatinine or urea nitrogen values ≥3 times Upper normal limit (ULN) at screening or baseline
* Moderate to severe hepatic impairment. Serum alanine transaminase (ALT) or aspartate transaminase levels ≥3 times ULN at screening or baseline
* Currently poorly controlled diabetes as indicated by HbA1c values \>9
* White blood cell (WBC) values \<3.5 K/μl
* History of paralytic ileus or current severe chronic constipation
* Known allergy to fasudil or established systemic inflammatory disease or autoimmune disease.
* Clinically significant hypotension defined by blood pressure values \<90/60 mmHg, regardless of the individual's sitting or standing position and associated with relevant clinical symptoms (e.g., tachycardia, dizziness, syncope)
* Current clinically significant depression or other mental disorder likely to affect cognition or interfere with study participation
* Recent (within 3 months) relevant medication changes. Participants must have been on stable anti-dementia (cholinesterase inhibitors or memantine) or anti-depressive medications for at least three months before the study
* Participants using sedating drugs, if unavoidable, will be excluded from the study. However, short-acting sleep medications can be used if taken as recommended and if the participant has maintained stability on them for a minimum of 3 months prior to the start of the study
* Participation in other drug trials
* Currently ongoing life-threatening disease, such as metastatic cancer, advanced cardiovascular disease, advanced respiratory disease, terminal kidney disease, or advanced stages of infectious diseases
* Any current or past neurological disease unrelated to Alzheimer's disease with cognitive sequelae
* A Corrected QT (QTc) interval ≥ 460 milliseconds for males or ≥ 470 milliseconds for females will be considered abnormal during the ECG assessments

Where this trial is running

Tromsø, Nordland and 5 other locations

• University Hospital of North Norway — Tromsø, Nordland, Norway (Not_yet_recruiting)
• Akershus Hospital: — Oslo, Oslo, Norway (Not_yet_recruiting)
• Haugesund Hospital — Haugesund, Rogaland, Norway (Not_yet_recruiting)
• Stavanger University Hospital — Stavanger, Rogaland, Norway (Recruiting)
• St. Olavs Hospital: — Trondheim, Trøndelag, Norway (Not_yet_recruiting)
• Haraldsplass Deaconess Hospital — Bergen, Vestland, Norway (Enrolling_by_invitation)

Study contacts

• Study coordinator: Dag Aarsland, PhD

Conditions Cognitive Decline, Mild; Alzheimer Disease; Mild Cognitive Decline; Fasudil