Randomized, Double-Blind, Placebo-Controlled 12-Month Study of Fasudil Hydrochloride in Patients with Early Alzheimer's Disease
- Trial ID
- 2023-506514-44-00
- Sponsor
- Helse Stavanger HF
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **efficacy** of fasudil 40 mg tds in preventing memory loss in individuals with early **Alzheimer's disease** (AD). This is clinically relevant as memory loss is a hallmark symptom of AD, and effective prevention could significantly improve patient outcomes and quality of life.
Secondary objectives include:
- Assessing the impact of fasudil on various cognitive measures, brain metabolism using FDG-PET, and relevant clinical features and biofluid biomarkers.
- Evaluating the safety and tolerability of fasudil 40 mg tds administered for up to 12 months in people with early AD.
- Assessing the efficacy of fasudil on brain pathology changes relevant to AD using validated fluid biomarkers.
- Evaluating additional exploratory clinical effects of fasudil 40 mg tds administered for up to 12 months in people with early AD.
Participants
The clinical trial involves participants diagnosed with **Alzheimer's disease**, specifically those in the early stages, such as Stage 3 Mild Cognitive Impairment (MCI) or Stage 4 mild Alzheimer's dementia. The study population includes both male and female subjects, with an age range starting from 50 years. Participants are required to have a significant change on a validated Alzheimer's disease amyloid or tau biomarker and a Clinical Dementia Rating (CDR) Global rating of 0.5 or 1.0. They must also have undergone an MRI scan within the past two years with no findings inconsistent with Alzheimer's disease. The trial does not involve a vulnerable population. Participants must be fluent in Norwegian and demonstrate adequate premorbid intellectual functioning. Female participants are required to be of non-childbearing potential or have a negative serum pregnancy test and agree to use effective birth control during the study. The sponsor has not provided information regarding the total number of participants. Participants are expected to have a reliable study partner for regular contact and must be capable of participating in all scheduled evaluations and completing all required tests.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **fasudil hydrochloride** in preventing memory loss in individuals with early Alzheimer's disease. This study is a randomized, double-blind, placebo-controlled trial with a parallel group design, conducted over a period of 12 months. Participants will be randomly assigned to receive either fasudil hydrochloride or a placebo, administered orally in capsule form. The trial aims to assess the primary outcome of changes in working memory over the 12-month period, using the FLAME computer-based working memory composite. Secondary outcomes include assessments of attention, executive function, and various biomarkers related to Alzheimer's disease.
The trial will commence with an inclusion (screening) visit, where potential participants will be evaluated against the principal inclusion criteria, which include a diagnosis of early Alzheimer's disease, significant changes in validated Alzheimer's biomarkers, and the capacity to provide informed consent. Participants must also have a reliable study partner and meet other criteria such as age and language fluency. Following successful screening, participants will be enrolled in the study and begin the treatment phase.
Throughout the trial, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments of vital signs, weight, physical and neurological examinations, and laboratory tests. The trial will also collect data on the ability to perform daily activities, overall clinical condition, and quality of life. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the long-term effects of the treatment.
The expected duration of participant involvement is 12 months, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is authorized to begin recruitment in June 2024, with an estimated end date in January 2028. Participants will be closely monitored throughout the study to ensure adherence to the protocol and to address any safety concerns promptly.
Treatment
The clinical trial involves the administration of **Fasudil Hydrochloride**, a **Rho-kinase (ROCK) inhibitor** with neuroprotective properties, for the treatment of early Alzheimer's disease. The experimental medication is provided in the form of a capsule, with two dosage regimens being evaluated. The first regimen involves a maximum daily dose of 120 mg, administered orally in divided doses over a 12-month period. The second regimen involves a maximum daily dose of 60 mg, also administered orally in divided doses over the same duration. The active substance, **fasudil hydrochloride**, is of chemical origin and is recognized for its potential therapeutic effects in neurodegenerative conditions.
In addition to the experimental medication, the study includes the use of placebo capsules designed to match the appearance of the fasudil capsules. These placebo capsules are utilized to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo capsules are formulated to match the 40 mg and 20 mg fasudil dosages, respectively, and are administered orally following the same schedule as the active treatment. The use of placebo controls is critical in assessing the efficacy of fasudil hydrochloride in preventing memory loss associated with early Alzheimer's disease.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. This monitoring is essential for maintaining the integrity of the study data and for accurately assessing the therapeutic potential of fasudil hydrochloride in the target population. The trial is conducted under authorized conditions, with all substances and procedures adhering to regulatory standards.
Efficacy
The efficacy of **Fasudil Hydrochloride** in the treatment of early Alzheimer's disease will be assessed through a placebo-controlled, randomized double-blind parallel group trial over a 12-month period. The primary endpoint for evaluating efficacy is the change in the FLAME computer-based working memory composite over the 12 months. Secondary endpoints include assessments using the FLAME battery to evaluate speed of attention, accuracy of attention, and executive function. Additionally, the trial will measure the extension and severity of the Alzheimer's disease hypometabolic pattern at FDG-PET, and changes in cerebrospinal fluid (CSF) and blood plasma biomarkers such as Aβ1-40, Aβ1-42, tau, p-tau, and Nfl over the same period.
Further secondary endpoints involve evaluating the ability to perform everyday activities using the Amsterdam ADL scale, overall clinical condition through the Clinical Global Impression of Change, and severity of dementia symptoms using the Clinical Dementia Rating (CDR)-sum of boxes. Neuropsychiatric symptoms and behaviors will be assessed with the Neuropsychiatric Inventory (NPI-Q), and quality of life will be evaluated using the DEMQOL and EQ-5D questionnaires. Safety data will be collected through measurements of vital signs, weight, physical and neurological examinations, clinical safety laboratory tests, ECG, and assessments of suicidality. These efficacy parameters will be collected and analyzed at specified intervals throughout the trial duration to determine the therapeutic impact of Fasudil Hydrochloride on early Alzheimer's disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Early AD, eg Stage 3 MCI or Stage 4 (mild AD dementia)
- 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 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
- 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 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 one months) relevant medication changes. Participants must have been on stable anti-dementia (cholinesterase inhibitors or memantine) or anti-depressive medications for at least one month 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 QTc interval ≥ 460 milliseconds for males or ≥ 470 milliseconds for females will be considered abnormal during the ECG assessments
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Recruiting | 01 Jan 2024 | 200 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo capsule to match 20 mg fasudil | Placebo | N/A | — | — | — | N/A |
Placebo capsule to match 40 mg fasudil | Placebo | N/A | — | — | — | N/A |
Fasudil Hyrdrochloride | Test | CAPSULE | ORAL | 60 | 12 | PRD10748355 |
Fasudil Hydrochloride | Test | CAPSULE | ORAL | 120 | 12 | PRD10748356 |