Cognitive Decline, MildPhase 2FEADNCT06362707
Fasudil Trial for Treatment of Early Alzheimer's Disease (FEAD)
A Phase 2 study testing Fasudil in people with Cognitive Decline, Mild and Alzheimer Disease, run by Helse Stavanger HF at 6 sites in Norway.
Trial summary
The goal of this placebo-controlled double-blind Phase 2 clinical trial is to test in people with early Alzheimer's Disease. The main questions it aims to answer are: Does treatment with fasudil, a ROCK-inhibitor, lead to significant improvement in working memory (based on computer-based working memory composite… Read more about this study
- Who is it for?
- Ages 50 to 100 years
- Conditions the study is for
- Cognitive Decline, Mild, Alzheimer Disease
- What is being tested?
- Fasudil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 6 sitesNorway
- Study dates
- 1 Aug 2024to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Norway6 sites, 6 recruiting
- Enrolling by invitation
Haraldsplass Deaconess Hospital
Bergen, Vestland
- Not yet recruiting
Haugesund Hospital
Haugesund, Rogaland
Arvid Rongve, PhD, +4752739000, arvid.rongve@helse-fonna.no
- Not yet recruiting
Akershus Hospital:
Oslo, Oslo
Tormod Fladby, PhD, +4767960000, tormod.fladby@medisin.uio.no
- Recruiting
Stavanger University Hospital
Stavanger, Rogaland
Dag Aarsland, PhD, +47975804, daarsland@gmail.com
Dag Aarsland, PhD
- Not yet recruiting
University Hospital of North Norway
Tromsø, Nordland
Ole Grønli, +4772626000, ole.kristian.gronli@unn.no
- Not yet recruiting
St. Olavs Hospital:
Trondheim, Trøndelag
John C Fløvig, +4772573000, john.chr.flovig@ntnu.no
About this study
Official title: A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease (FEAD)
The goal of this placebo-controlled double-blind Phase 2 clinical trial is to test in people with early Alzheimer's Disease.
The main questions it aims to answer are:
Read more
- Does treatment with fasudil, a ROCK-inhibitor, lead to significant improvement in working memory (based on computer-based working memory composite scores) compared to placebo in individuals with early Alzheimer's disease (AD) over 12 months?
- What is the effect of fasudil treatment for 12 months on other cognitive functions, brain metabolism measured by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), and other relevant clinical functions and biomarkers in individuals with early Alzheimer's disease (AD)?
- Treatment will be escalated to a maintenance dose of 120 mg total daily dose for up to 50 weeks, with regular clinic visits for efficacy and safety evaluations.
- Assessments will include cognitive tests, FDG-PET scans, and biomarker analyses, with follow-up by the Data and Safety Monitoring Board for ongoing safety review.
The study will compare participants receiving fasudil with those receiving placebo to see if fasudil treatment leads to improvements in cognitive functions, brain metabolism measured by FDG-PET.
Read the detailed description
This is a 2-arm, parallel-group, 12-month, randomized, placebo-controlled double-blind Phase 2 trial of fasudil in up to 200 people with early AD. Fasudil is a ROCK-inhibitor (rho-associated protein kinase inhibitor), a vasodilator that is approved for treating vasospasms following subarachnoidal bleeding in Japan and China. The drug has acceptable safety and tolerability and has been shown to protect neurons and synapses in animal models of AD. Eligible participants must have Stage 3-4 mild cognitive impairment (MCI) or mild dementia due to AD, as recently defined by FDA Guidance, and have shown a significant change on a validated AD biomarker (e.g. amyloid PET scans or CSF Aβ 1-42 or blood p-tau 217 levels). In addition, they must have a CDR Global rating of 0.5 or 1.0 and an MRI scan within the past two years that has no findings inconsistent with AD.
People who meet all inclusion criteria will be enrolled in three successive cohorts of 20, 50, and 130 people, respectively. Participants will be randomized 1:1 to receive fasudil or a matching placebo. All participants will undergo a 2-week titration period at a total daily dose of 60 mg (20 mg tds) before being escalated to the maintenance dose of 120 mg total daily dose (40 mg tds) for up to 50 additional weeks of treatment. The selected dose of 120 mg per day is optimized for potential efficacy over the planned 12-month treatment while providing a reasonable margin of safety based on available clinical and nonclinical data. Participants will visit the clinic for efficacy and/or safety evaluations at 2-week intervals for the first month and then monthly thereafter (see Table 1. Schedule of Assessments).
The Data and Safety Monitoring Board (DSMB) will perform an unblinded review of the safety and pharmacokinetic (PK) data once all ongoing patients in Cohort 1 have completed at least 3 months of treatment and make recommendations to the study team that may include stopping or continuing the study (with or without changes to the study procedures).
The DSMB will continue to review all data available from Cohorts 1-3 for the remainder of the study at 3-monthly intervals, or more frequently if warranted by emergent data, and recommend any changes to the study procedures to ensure appropriate safety oversight and management of study participants through completion of the study.
The primary efficacy outcome is the FLAME (Factors of Longitudinal Attention, Memory and Executive Function) computer-based working memory composite. The key secondary outcomes are based on the expression of the AD-like hypometabolic pattern on FDG-PET and additional cognitive tests from the FLAME battery, including memory, working memory, attention, and executive functions. Additional secondary outcomes include CSF and blood-based AD biomarkers, and clinical measures including Clinical Global Impression of Change (CGIC), and Clinical Dementia Rating (CDR), neuropsychiatric symptoms (NPI), instrumental activities of daily living (Amsterdam IADL scale) and quality of life (DEMQOL). Standard safety measures include monthly assessments of adverse events (AEs), vital signs, and laboratory tests (including blood and urine analyses) as well as ECGs and the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Conditions
- Cognitive Decline, Mild, Alzheimer Disease
- Being tested
- Fasudil, Placebo
- Keywords
- Alzheimer Disease, Mild Cognitive Decline, Fasudil
- Medical subject headings
- Cognitive Dysfunction, Lymphoma, Follicular, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FasudilDrug
A ROCK inhibitor approved for treating vasospasms following subarachnoidal bleeding in Japan and China. Dosage: Participants will undergo a 2-week titration period at 60 mg daily before escalating to a maintenance dose of 120 mg daily.
PlaceboDrug
Placebo tablets that look identical to the fasudil tablets and will follow the same dosing schedule as participants receiving fasudil.
| Study group | Role | What they receive |
|---|---|---|
| Fasudil | Experimental | In recognition that fasudil has only been evaluated in published studies for treatment durations of up to 3 months, we intend to enroll participants in three successive cohorts of 20, 50 and 130 people, respectively. Participants in the initial cohort will undergo a 2-week titration period (60 mg total daily dose; 20 mg tds) before being escalated to the maintenance dose (120 mg total daily dose; 40 mg tds) for up to 50 additional weeks of treatment. The selected dose of 120mg per day is optimized for potential efficacy over the planned 12-month treatment period, while providing a reasonable margin of safety based on available clinical and nonclinical data. Receives: Drug: Fasudil |
| Placebo | Placebo comparator | Following screening procedures, subjects will be randomized at baseline to receive fasudil or matching placebo across all cohorts. 1:1 randomization will be performed. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognition
The primary outcome will be the FLAME computer-based working memory composite comprised of tests of working memory and episodic memory
Measured: The cognitive battery will be performed at baseline and every three months until last visit, supported by trial staff (up to 1 year).
Brain metabolism
FDG-PET is a highly sensitive means of determining brain metabolism and has been accepted as a good proxy measure of synaptic function. Importantly, FDG-PET based measures of brain metabolism correlate well with cognitive decline in AD, better than amyloid plaques. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study suggest that FDG PET has good power to detect a 25% treatment effect over 12 months
Measured: The outcome will be change in FDG-PET between baseline and at 12 months.
Secondary outcomes (23)
Plasma levels of ptau217
This study involves the collection of blood samples, following standardized procedures. Blood markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features to fulfill inclusion criteria. The primary focus will be on examining changes in levels of plasma ptau217 and nfl, measured in pg/mL.
Measured: Collection of blood samples will occur at baseline and the 12-month visit.
Plasma levels of nfl
This study involves the collection of blood samples, following standardized procedures. Blood markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features to fulfill inclusion criteria. The primary focus will be on examining changes in levels of plasma ptau217 and nfl, measured in pg/mL.
Measured: Collection of blood samples will occur at baseline and the 12-month visit.
Levels of cerebrospinal Aβ1-40 and Aβ1-42
This study involves the collection of cerebrospinal fluid (CSF) samples, following standardized procedures. CSF markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features, measured in pg/mL.
Measured: Collection of CSF samples will occur at baseline and the 12-month visit.
Levels of cerebrospinal tau and p-tau
This study involves the collection of cerebrospinal fluid (CSF) samples, following standardized procedures. CSF markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features, measured in pg/mL.
Measured: Collection of CSF samples will occur at baseline and the 12-month visit.
Blood pressure (Safety assessments)
Safety measurements, blood pressure measured in millimetres of mercury (mmHg).
Measured: Conducted at all visits throughout the 12-month duration of the study. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at screening, month 6, and month 12
Pulse (Safety assessments)
Safety measurements, including pulse frequency in beats per minute (bpm).
Measured: Conducted at all visits throughout the 12-month duration of the study.
Urine testing (Safety assessments)
Urine will be tested with a dipstick test to explore proteinuria or hematuria.
Measured: Conducted at baseline and all visits throughout the 12-month duration of the study.
Blood urea nitrogen (BUN) (Safety assessments)
Measured in blood in mmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Potassium (Safety assessments)
Measured in blood in mmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Sodium (Safety assessments)
Measured in blood in mmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Calcium (Safety assessments)
Measured in blood in mmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Glucose (Safety assessments)
Measured in blood in mmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Hemoglobin (Safety assessments)
Measured in blood in g/dL
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Creatinine (Safety assessments)
Measured in blood in μmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Total and direct bilirubin (Safety assessments)
Measured in blood in μmol/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
CRP (C-reactive protein) (Safety assessments)
Measured in blood in mg/L
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Aspartate aminotransferase (AST) (Safety assessments)
Measured in blood in U/L (units per liter)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Serum glutamic-oxaloacetic transaminase (SGOT) (Safety assessments)
Measured in blood in U/L (units per liter)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Alanine aminotransferase (ALT) (Safety assessments)
Measured in blood in U/L (units per liter)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Serum glutamic-pyruvic transaminase (SGPT) (Safety assessments)
Measured in blood in U/L (units per liter)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Alkaline phosphatase (Safety assessments)
Measured in blood in U/L (units per liter)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Electrocardiogram (ECG) (Safety assessments)
Measurement of ECG QT Interval in ms (milliseconds)
Measured: Conducted at baseline and all monthly visits throughout the 12-month duration of the study. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at screening, month 6, and month 12
Columbia Suicide Severity Rating Scale (C-SSRS) (Safety assessments)
Participants will be monitored appropriately and observed for suicidal ideation and unusual behavior.
Measured: Screening visit, month 6 and 12 months visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2024
- Study start1 Aug 2024
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Cognitive Decline, MildStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helse Stavanger HF
- Sponsor type
- Other government
- Collaborators
- University of Exeter, Helse Fonna, St. Olavs Hospital, University Hospital, Akershus, Haraldsplass Deaconess Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06362707
- Sponsor's protocol ID
- 2023161001
- Acronym
- FEAD
- Status last verified
- Apr 2026
- First submitted
- 2 Feb 2024
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Asano T, Ikegaki I, Satoh S, Suzuki Y, Shibuya M, Takayasu M, Hidaka H. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther. 1987 Jun;241(3):1033-40.
PubMed 3598899Atri A, Frolich L, Ballard C, Tariot PN, Molinuevo JL, Boneva N, Windfeld K, Raket LL, Cummings JL. Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials. JAMA. 2018 Jan 9;319(2):130-142. doi: 10.1001/jama.2017.20373.
PubMed 29318278Ballard C, Atri A, Boneva N, Cummings JL, Frolich L, Molinuevo JL, Tariot PN, Raket LL. Enrichment factors for clinical trials in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2019 May 20;5:164-174. doi: 10.1016/j.trci.2019.04.001. eCollection 2019.
PubMed 31193334Ballard C, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Williams G, Doherty P, Corbett A, Sultana J. Drug repositioning and repurposing for Alzheimer disease. Nat Rev Neurol. 2020 Dec;16(12):661-673. doi: 10.1038/s41582-020-0397-4. Epub 2020 Sep 16.
PubMed 32939050Brooker H, Williams G, Hampshire A, Corbett A, Aarsland D, Cummings J, Molinuevo JL, Atri A, Ismail Z, Creese B, Fladby T, Thim-Hansen C, Wesnes K, Ballard C. FLAME: A computerized neuropsychological composite for trials in early dementia. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12098. doi: 10.1002/dad2.12098. eCollection 2020.
PubMed 33088895Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, Kearns I, Kehoe P, Mudher A, Passmore A, Shepherd N, Walsh F, Ballard C. Drug repositioning for Alzheimer's disease. Nat Rev Drug Discov. 2012 Nov;11(11):833-46. doi: 10.1038/nrd3869.
PubMed 23123941Couch BA, DeMarco GJ, Gourley SL, Koleske AJ. Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration. J Alzheimers Dis. 2010;20(4):1003-8. doi: 10.3233/JAD-2010-091114.
PubMed 20413901Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, Ballard C. The Effect of an Online Cognitive Training Package in Healthy Older Adults: An Online Randomized Controlled Trial. J Am Med Dir Assoc. 2015 Nov 1;16(11):990-7. doi: 10.1016/j.jamda.2015.06.014.
PubMed 26543007Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308.
PubMed 7991117Elliott C, Rojo AI, Ribe E, Broadstock M, Xia W, Morin P, Semenov M, Baillie G, Cuadrado A, Al-Shawi R, Ballard CG, Simons P, Killick R. A role for APP in Wnt signalling links synapse loss with beta-amyloid production. Transl Psychiatry. 2018 Sep 20;8(1):179. doi: 10.1038/s41398-018-0231-6.
PubMed 30232325Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149(2):351-6. doi: 10.2214/ajr.149.2.351.
PubMed 3496763Fukumoto Y, Yamada N, Matsubara H, Mizoguchi M, Uchino K, Yao A, Kihara Y, Kawano M, Watanabe H, Takeda Y, Adachi T, Osanai S, Tanabe N, Inoue T, Kubo A, Ota Y, Fukuda K, Nakano T, Shimokawa H. Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension. Circ J. 2013;77(10):2619-25. doi: 10.1253/circj.cj-13-0443. Epub 2013 Aug 3.
PubMed 23912836Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frolich L, Schonknecht P, Ito K, Mielke R, Kalbe E, Zundorf G, Delbeuck X, Pelati O, Anchisi D, Fazio F, Kerrouche N, Desgranges B, Eustache F, Beuthien-Baumann B, Menzel C, Schroder J, Kato T, Arahata Y, Henze M, Heiss WD. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage. 2002 Sep;17(1):302-16. doi: 10.1006/nimg.2002.1208.
PubMed 12482085Hinderling PH, Karara AH, Tao B, Pawula M, Wilding I, Lu M. Systemic availability of the active metabolite hydroxy-fasudil after administration of fasudil to different sites of the human gastrointestinal tract. J Clin Pharmacol. 2007 Jan;47(1):19-25. doi: 10.1177/0091270006293767.
PubMed 17192498Ido K, Kurogi R, Kurogi A, Nishimura K, Arimura K, Nishimura A, Ren N, Kada A, Matsuo R, Onozuka D, Hagihara A, Takagishi S, Yamagami K, Takegami M, Nohara Y, Nakashima N, Kamouchi M, Date I, Kitazono T, Iihara K; J-ASPECT Study Collaborators. Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older. PLoS One. 2020 Apr 9;15(4):e0230953. doi: 10.1371/journal.pone.0230953. eCollection 2020.
PubMed 32271814
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease (FEAD)
- ClinicalTrials.gov ID
- NCT06362707
- Acronym / sponsor ID
- FEAD / 2023161001
- Conditions
- Cognitive Decline, Mild, Alzheimer Disease
- Keywords
- Alzheimer Disease, Mild Cognitive Decline, Fasudil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Helse Stavanger HFOther government
- Collaborators
- University of Exeter, Helse Fonna, St. Olavs Hospital, University Hospital, Akershus, Haraldsplass Deaconess Hospital
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 12 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this placebo-controlled double-blind Phase 2 clinical trial is to test in people with early Alzheimer's Disease.
The main questions it aims to answer are:
- Does treatment with fasudil, a ROCK-inhibitor, lead to significant improvement in working memory (based on computer-based working memory composite scores) compared to placebo in individuals with early Alzheimer's disease (AD) over 12 months?
- What is the effect of fasudil treatment for 12 months on other cognitive functions, brain metabolism measured by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), and other relevant clinical functions and biomarkers in individuals with early Alzheimer's disease (AD)?
- Treatment will be escalated to a maintenance dose of 120 mg total daily dose for up to 50 weeks, with regular clinic visits for efficacy and safety evaluations.
- Assessments will include cognitive tests, FDG-PET scans, and biomarker analyses, with follow-up by the Data and Safety Monitoring Board for ongoing safety review.
The study will compare participants receiving fasudil with those receiving placebo to see if fasudil treatment leads to improvements in cognitive functions, brain metabolism measured by FDG-PET.
Detailed description
This is a 2-arm, parallel-group, 12-month, randomized, placebo-controlled double-blind Phase 2 trial of fasudil in up to 200 people with early AD. Fasudil is a ROCK-inhibitor (rho-associated protein kinase inhibitor), a vasodilator that is approved for treating vasospasms following subarachnoidal bleeding in Japan and China. The drug has acceptable safety and tolerability and has been shown to protect neurons and synapses in animal models of AD. Eligible participants must have Stage 3-4 mild cognitive impairment (MCI) or mild dementia due to AD, as recently defined by FDA Guidance, and have shown a significant change on a validated AD biomarker (e.g. amyloid PET scans or CSF Aβ 1-42 or blood p-tau 217 levels). In addition, they must have a CDR Global rating of 0.5 or 1.0 and an MRI scan within the past two years that has no findings inconsistent with AD.
People who meet all inclusion criteria will be enrolled in three successive cohorts of 20, 50, and 130 people, respectively. Participants will be randomized 1:1 to receive fasudil or a matching placebo. All participants will undergo a 2-week titration period at a total daily dose of 60 mg (20 mg tds) before being escalated to the maintenance dose of 120 mg total daily dose (40 mg tds) for up to 50 additional weeks of treatment. The selected dose of 120 mg per day is optimized for potential efficacy over the planned 12-month treatment while providing a reasonable margin of safety based on available clinical and nonclinical data. Participants will visit the clinic for efficacy and/or safety evaluations at 2-week intervals for the first month and then monthly thereafter (see Table 1. Schedule of Assessments).
The Data and Safety Monitoring Board (DSMB) will perform an unblinded review of the safety and pharmacokinetic (PK) data once all ongoing patients in Cohort 1 have completed at least 3 months of treatment and make recommendations to the study team that may include stopping or continuing the study (with or without changes to the study procedures).
The DSMB will continue to review all data available from Cohorts 1-3 for the remainder of the study at 3-monthly intervals, or more frequently if warranted by emergent data, and recommend any changes to the study procedures to ensure appropriate safety oversight and management of study participants through completion of the study.
The primary efficacy outcome is the FLAME (Factors of Longitudinal Attention, Memory and Executive Function) computer-based working memory composite. The key secondary outcomes are based on the expression of the AD-like hypometabolic pattern on FDG-PET and additional cognitive tests from the FLAME battery, including memory, working memory, attention, and executive functions. Additional secondary outcomes include CSF and blood-based AD biomarkers, and clinical measures including Clinical Global Impression of Change (CGIC), and Clinical Dementia Rating (CDR), neuropsychiatric symptoms (NPI), instrumental activities of daily living (Amsterdam IADL scale) and quality of life (DEMQOL). Standard safety measures include monthly assessments of adverse events (AEs), vital signs, and laboratory tests (including blood and urine analyses) as well as ECGs and the Columbia-Suicide Severity Rating Scale (C-SSRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fasudil | Experimental | Drug: FasudilIn recognition that fasudil has only been evaluated in published studies for treatment durations of up to 3 months, we intend to enroll participants in three successive cohorts of 20, 50 and 130 people, respectively. Participants in the initial cohort will undergo a 2-week titration period (60 mg total daily dose; 20 mg tds) before being escalated to the maintenance dose (120 mg total daily dose; 40 mg tds) for up to 50 additional weeks of treatment. The selected dose of 120mg per day is optimized for potential efficacy over the planned 12-month treatment period, while providing a reasonable margin of safety based on available clinical and nonclinical data. |
| Placebo | Placebo comparator | Drug: PlaceboFollowing screening procedures, subjects will be randomized at baseline to receive fasudil or matching placebo across all cohorts. 1:1 randomization will be performed. |
Who may qualify
- Ages
- 50 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FasudilA ROCK inhibitor approved for treating vasospasms following subarachnoidal bleeding in Japan and China. Dosage: Participants will undergo a 2-week titration period at 60 mg daily before escalating to a maintenance dose of 120 mg daily. | Drug | Fasudil |
| PlaceboPlacebo tablets that look identical to the fasudil tablets and will follow the same dosing schedule as participants receiving fasudil. | Drug | Placebo |
Primary outcome
Cognition
Time frame: The cognitive battery will be performed at baseline and every three months until last visit, supported by trial staff (up to 1 year).
The primary outcome will be the FLAME computer-based working memory composite comprised of tests of working memory and episodic memory
Brain metabolism
Time frame: The outcome will be change in FDG-PET between baseline and at 12 months.
FDG-PET is a highly sensitive means of determining brain metabolism and has been accepted as a good proxy measure of synaptic function. Importantly, FDG-PET based measures of brain metabolism correlate well with cognitive decline in AD, better than amyloid plaques. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study suggest that FDG PET has good power to detect a 25% treatment effect over 12 months
23 secondary outcomes
Plasma levels of ptau217
Time frame: Collection of blood samples will occur at baseline and the 12-month visit.
Plasma levels of nfl
Time frame: Collection of blood samples will occur at baseline and the 12-month visit.
Levels of cerebrospinal Aβ1-40 and Aβ1-42
Time frame: Collection of CSF samples will occur at baseline and the 12-month visit.
Levels of cerebrospinal tau and p-tau
Time frame: Collection of CSF samples will occur at baseline and the 12-month visit.
Blood pressure (Safety assessments)
Time frame: Conducted at all visits throughout the 12-month duration of the study. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at screening, month 6, and month 12
Pulse (Safety assessments)
Time frame: Conducted at all visits throughout the 12-month duration of the study.
Urine testing (Safety assessments)
Time frame: Conducted at baseline and all visits throughout the 12-month duration of the study.
Blood urea nitrogen (BUN) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Potassium (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Sodium (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Calcium (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Glucose (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Hemoglobin (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Creatinine (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Total and direct bilirubin (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
CRP (C-reactive protein) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Aspartate aminotransferase (AST) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Serum glutamic-oxaloacetic transaminase (SGOT) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Alanine aminotransferase (ALT) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Serum glutamic-pyruvic transaminase (SGPT) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Alkaline phosphatase (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study.
Electrocardiogram (ECG) (Safety assessments)
Time frame: Conducted at baseline and all monthly visits throughout the 12-month duration of the study. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at screening, month 6, and month 12
Columbia Suicide Severity Rating Scale (C-SSRS) (Safety assessments)
Time frame: Screening visit, month 6 and 12 months visits
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 3598899Asano T, Ikegaki I, Satoh S, Suzuki Y, Shibuya M, Takayasu M, Hidaka H. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther. 1987 Jun;241(3):1033-40.
- Background: PubMed 29318278Atri A, Frolich L, Ballard C, Tariot PN, Molinuevo JL, Boneva N, Windfeld K, Raket LL, Cummings JL. Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials. JAMA. 2018 Jan 9;319(2):130-142. doi: 10.1001/jama.2017.20373.
- Background: PubMed 31193334Ballard C, Atri A, Boneva N, Cummings JL, Frolich L, Molinuevo JL, Tariot PN, Raket LL. Enrichment factors for clinical trials in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2019 May 20;5:164-174. doi: 10.1016/j.trci.2019.04.001. eCollection 2019.
- Background: PubMed 32939050Ballard C, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Williams G, Doherty P, Corbett A, Sultana J. Drug repositioning and repurposing for Alzheimer disease. Nat Rev Neurol. 2020 Dec;16(12):661-673. doi: 10.1038/s41582-020-0397-4. Epub 2020 Sep 16.
- Background: PubMed 33088895Brooker H, Williams G, Hampshire A, Corbett A, Aarsland D, Cummings J, Molinuevo JL, Atri A, Ismail Z, Creese B, Fladby T, Thim-Hansen C, Wesnes K, Ballard C. FLAME: A computerized neuropsychological composite for trials in early dementia. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12098. doi: 10.1002/dad2.12098. eCollection 2020.
- Background: PubMed 23123941Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, Kearns I, Kehoe P, Mudher A, Passmore A, Shepherd N, Walsh F, Ballard C. Drug repositioning for Alzheimer's disease. Nat Rev Drug Discov. 2012 Nov;11(11):833-46. doi: 10.1038/nrd3869.
- Background: PubMed 20413901Couch BA, DeMarco GJ, Gourley SL, Koleske AJ. Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration. J Alzheimers Dis. 2010;20(4):1003-8. doi: 10.3233/JAD-2010-091114.
- Background: PubMed 26543007Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, Ballard C. The Effect of an Online Cognitive Training Package in Healthy Older Adults: An Online Randomized Controlled Trial. J Am Med Dir Assoc. 2015 Nov 1;16(11):990-7. doi: 10.1016/j.jamda.2015.06.014.
- Background: PubMed 7991117Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308.
- Background: PubMed 30232325Elliott C, Rojo AI, Ribe E, Broadstock M, Xia W, Morin P, Semenov M, Baillie G, Cuadrado A, Al-Shawi R, Ballard CG, Simons P, Killick R. A role for APP in Wnt signalling links synapse loss with beta-amyloid production. Transl Psychiatry. 2018 Sep 20;8(1):179. doi: 10.1038/s41398-018-0231-6.
- Background: PubMed 3496763Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149(2):351-6. doi: 10.2214/ajr.149.2.351.
- Background: PubMed 23912836Fukumoto Y, Yamada N, Matsubara H, Mizoguchi M, Uchino K, Yao A, Kihara Y, Kawano M, Watanabe H, Takeda Y, Adachi T, Osanai S, Tanabe N, Inoue T, Kubo A, Ota Y, Fukuda K, Nakano T, Shimokawa H. Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension. Circ J. 2013;77(10):2619-25. doi: 10.1253/circj.cj-13-0443. Epub 2013 Aug 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fasudil in people with Cognitive Decline, Mild and Alzheimer Disease, run by Helse Stavanger HF at 6 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dag Aarsland, PhD (+4797575804, daarsland@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognition (time frame: The cognitive battery will be performed at baseline and every three months until last visit, supported by trial staff (up to 1 year).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06362707, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.