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