Fasudil Trial for Treatment of Early Alzheimer's Disease (FEAD)

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