Memory Clinic

Merck

A Phase 2 Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of MK-2214 in Participants with Early Alzheimer's Disease.

MK-2214 is a humanized anti-tau mAb, which targets a specific phosphorylation epitope at serine 413 that is detected on oligomeric tau species found in the brains of AD patients.

Treatment Period: 104 weeks

IV Q4w

Site Enrollment Status: Under REB review

Inclusion

• Age 50-85
• MMSE score between 24-30
• Biomarker evidence of AD amyloid pathology as demonstrated by one of the following at Screening:
  • Blood-based biomarker assay (current or historical) OR
  • CSF-based biomarker assay (current or historical) OR
  • Amyloid PET (historical)
• Global CDR score of 0.5 or 1 and a memory box score greater than or equal to 0.5 at Screening

Exclusion

Prior treatment with:

• Anti-amyloid agents (eg, tarenflurbil, tramiprosate)
• Anti-tau agents (eg, tilavonemab, BIIB-080)
• Anti-amyloid antibodies (eg, bapineuzumab, aducanumab, lecanemab, donanemab)

Novartis

A randomized, placebo-controlled, parallel group, 72-week study to evaluate the efficacy and safety of VHB937 in participants with early Alzheimer's Disease followed by an Extension.

Phase II

Treatment Period: Treatment period: 144 W( 68 w DBL and 76 w OLE)

IV Q4W

Site Enrollment Status: Under REB review

Inclusion

• 50 to 85 years of age
• ADAS-Cog14 total score between 13 and 54 (inclusive) at Screening
• CDR Global score of 0.5 or 1.0 at Screening and Baseline

Exclusion

Prior or current treatment with an anti-amyloid antibody.

Roche:Trontier 1

A phase III, Multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy and safety study of trontinemab in participants with early symptomatic Alzheimer's Disease (MCI to mild dementia due toAD)

Trontinemab (RO7126209) is a 2+1 bispecific monoclonal antibody (mAb) construct that combines, through recombinant fusion, the anti-amyloid-beta (A) antibody gantenerumab with a Brainshuttle module that specifically binds to the human transferrin receptor 1 (TfR1)

Induction Dose: IV Q4w for 24 weeks

Maintenance Dose: IVQ12 w for 47 w( w25-72)

Site Enrollment Status: Under REB review

Inclusion

• Age 50-90
• MMSE score ≥ 22
• CDR-GS of 0.5 or 1.0
• Evidence of AD pathological process, as confirmed on amyloid PET scan, visual read by the core/central PET laboratory. A CSF tau181/Aβ42 ratio may be used as an alternative option if amyloid PET is not available

Exclusion

• Any previous or current use of passive immunotherapy (immunoglobulin) or other long-acting biologic agent that is approved or under evaluation, or has been evaluated to prevent or postpone cognitive decline
• Any other investigational treatment within 5 half-lives or 4 months prior to screening, whichever is longer
• IV immunoglobulin therapy within 5 half-lives or 4 months prior to baseline, whichever is longer
• Anticoagulation medications at screening, and there should be no plans to initiate any prior to or after randomization

Roche: Traveller

Master Screening Study To Determine Individuals With Potential Trial Eligibility For Alzheimer's Disease Studies As Assessed By Biomarker Status And Cognition.

No investigational medicinal product (IMP) is administered in this study. The overarching structure of this study is a flexible master pre-screening process that will assess participants' potential eligibility for a Roche interventional Alzheimer's disease (AD) study based on a cognitive test and plasma levels of pTau217.

Site Enrollment Status: Under REB review

Inclusion

• Age 50-90
• Report of objective or subjective memory concerns (by the participant and/or their informant) within the last year with or without a previous clinical diagnosis of MCI or dementia due to AD

Exclusion

Previous AD diagnosis based on biomarker confirmation with an approved or validated method (e.g., Amyloid PET or CSF) is exclusionary

Roche-Phase 1

Protocol: BP45770

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Single Ascending Dose Study To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Ro7812653 Following Intrathecal Administration In Participants With Early Symptomatic Alzheimer's Disease.

RO7812653 is an intrathecally (IT) administered antisense oligonucleotide (ASO) that selectively induces the degradation of the apolipoprotein E (APOE) mRNA transcript (all variants), through Ribonuclease H mediated degradation, and is anticipated to reduce ApoE protein expression in the central nervous system (CNS).

Site Enrollment Status: Under REB review

Inclusion

• Age ≥50 and ≤75 years
• CDR-GS of 0.5 or 1.0
• Evidence of AD pathological process, as confirmed by the p-tau 181/Aβ1-42 ratio CSF test or Aβ PET

Exclusion

• Participating in any other ApoE-targeting clinical trials prior to screening
• Current enrollment or past participation in a clinical study involving an investigational study treatment or any other type of interventional medical research within five half-lives or six months before the screening, whichever is longer
• Use of any passive immunotherapy (immunoglobulin) or other long-acting biologic agent that is approved or under evaluation (unless confirmed to have received placebo) to prevent or postpone cognitive decline within 52 weeks before randomization

AriBio

A Phase 3 Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants with Early Alzheimer's Disease.

AR1001 is a novel pyrrolo-pyrimidinone compound that demonstrates potent, reversible, and selective phosphodiesterase-5 (PDE-5) inhibition.

Treatment Period: 52 weeks

Oral, QD

Optional OLE: 52 w

Site Enrollment Status: Recruitment closed

Inclusion

• Age 55 to 90
• MMSE ≥ 20
• Positive biomarker for brain amyloid pathology as indicated by assessment of at least one of the following:
  • Current or historic CSF with Lumipulse beta-amyloid ratio [1-42/1-40] ≤ 0.072 or Elecsys p-tau 181/Aβ[1-42] ≤ 0.028
  • Historic amyloid positron emission tomography (PET) assessment of imaging agent uptake into the brain is acceptable to determine eligibility (PET confirmed by central read)
• CDR-GS of 0.5 to 1.0
• Must be stable for at least three months (12 weeks) prior to baseline

Exclusion

• Participants who have been and/or are currently being treated with anti-amyloid, anti-tau, or any other investigational therapies for AD
• History of myocardial infarction, unstable angina, coronary artery disease, and/or New York Heart Association (NYHA) class III or IV heart failure within the last 12 months
• Participants taking an oral cholinesterase inhibitor and/or memantine not on a stable dose for at least 3 months prior to screening. Treatment and dosing should remain stable, with no changes throughout the trial
• Participants who currently take any other PDE-5 inhibitors (e.g., sildenafil)

Passage Bio

A Phase 1b open-label, multicenter, dose escalation study to assess the safety, tolerability and pharmacodynamic effects of a single dose of pbft02 delivered into the cisterna magna(icm) of adult subjects with frontotemporal dementia (FTD) and mutations in the progranulin gene (GRN).

Site Enrollment Status: Open

Inclusion

• Age ≥ 35 and ≤ 75
• Documented to be a GRN mutation carrier
• Clinical diagnosis according to current international consensus diagnostic criteria of possible bvFTD or PPA (nfvPPA, [svPPA, or lvPPA)
• Plasma NfL level > 50 pg/mL
• CDR plus NACC FTLD global score of 0.5 or 1.0

Exclusion

• Biomarker evidence of AD
• Classification of the GRN mutation as “not pathogenic,” “likely benign variant,” “benign variant,” or “pathogenic nature unclear” in the AD
• Previous treatment with any gene therapy
• Rosen-modified HIS score ≥ 7
• Previous treatment with any gene therapy
• History of untreated B12 deficiency
• Unregulated hypothyroidism
• Use of anticoagulants in the 2 weeks prior to screening, or anticipated use of anticoagulants during the study is exclusionary
• Serum creatinine > 2 mg/dL

CRND-TorCA

Improving prognostic confidence in neurodegenerative diseases causing dementia using peripheral biomarkers and integrative modelling.

Observational

Site Enrollment Status: Active to recruitment

Inclusion

• Age 30- 95
• Referring diagnosis of possible or probable MCI or dementia
• Have a reliable study partner who has frequent contact with participants, can come to study visits and provide information about them

Exclusion

• Participant is incompatible with neuropsychology assessments
• Patients who do not have a caregiver who would be able to participate in the study

Empathy Study

A pilot study assessing the benefits of a dementia caregiver educational brochure on decreased empathy and emotion recognition in patients with neurodegenerative disease.

Observational

Site Enrollment Status: Active to recruitment

Inclusion

• Both patient and caregiver must be aged 50-95 (inclusive)
• MOCA 10-25
• Must have a diagnosis of one of the following conditions:
  • Alzheimer's Disease
  • Parkinson's Disease/Dementia with Lewy Body
  • Frontotemporal Lobar Degeneration-syndromes
  • Vascular Dementia

Exclusion

• Not English speaking
• Patients who do not have a caregiver who would be able to participate in the study

ALLFTD

ARTFL-LEFFTDS LONGITUDINAL FRONTOTEMPORAL LOBAR DEGENERATION

Observational

Site Enrollment Status: On Hold

Please note that visit scheduling will be paused on/after May 1, 2025, due to pending grant status.

Inclusion

• 18 years old or older
• Have a reliable study partner
• Be able to read, understand, and speak English
• Strong history of an FTLD syndrome OR a patient with the diagnosis of:
  • Frontotemporal dementia (FTD)
  • Corticobasal syndrome (CBS)
  • Progressive supranuclear palsy (PSP)
  • Primary progressive aphasia (PPA)
  • Behavioural variant FTD

Exclusion

• Known presence of a structural brain lesion (e.g., tumour, cortical infarct) that could reasonably explain symptoms in a symptomatic participant
• Known presence of an Alzheimer's disease
• A previous history of Korsakoff encephalopathy
• Uncorrected B12 deficiency

NABILONE-FTD

Double Blind Crossover Clinical Trial of Nabilone for Agitation in Frontotemporal Dementia

Treatment Period: 14 weeks

• 6 weeks of Nabilone
• 6 weeks of placebo
• 3-week washout between treatment periods

Nabilone (oral THC) daily:

• Initially will be taken once a day
• Will increase to twice daily after a week
• Dose will increase from 0.5mg daily up to 4mg daily across the first 4 weeks of treatment

Site Enrollment Status: Active

Inclusion

• 18 years old or older
• Major neurocognitive disorder due to probable bvFTD or PPA
• Meets International Psychogeriatric Association criteria for agitation in cognitive disorders
• CMAI score of 39 or above
• Stable psychoactive medication for 1 month prior to screening (all medications allowed) with no intention to change dose during treatment period
• Available study partner with ≥10 hours per week in-person contact with the patient

Exclusion

• NPI domain score (severity x frequency) ≥4 on the delusions or hallucinations subscale
• Clinically significant orthostatic hypotension
• Symptomatic orthostatic tachycardia
• Unstable cardiovascular condition in the opinion of the investigator
• Known or suspected history of drug or alcohol dependence or abuse in the past 12 months, including use of any psychomimetic drugs
• Allergy, or significant adverse reaction to cannabinoids
• Major depressive episode within 6 months of screening
• Women who are breastfeeding or pregnant
• Other psychiatric or neurological condition that could cause significant agitation
• Ongoing use of any cannabinoid-related products

4RTNI-2: 4-Repeat Tauopathy Neuroimaging Initiative – Cycle 2

This is an observational study which aims to determine the natural history of insoluble tau deposition as measured by PET scans in Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) patients as compared to age-matched normal elders, quantify the longitudinal changes in cerebrospinal fluid as compared with other fluid biomarkers of neurodegeneration, measure ocular neuronal injury markers over time and to determine the clinical, MRI and neuronal injury marker correlates of tau deposition measured by PET.

Participants and their caregivers are asked to come in for 3 visits every 6 months for baseline, 6-month and 12-month visits. A select group of participants (those diagnosed to have oligo  variant PSP and healthy controls) will be asked to come back for a 24-month visit. Each visit will take 2-3 full days to complete and will involve the following assessments: MRI scan, PET scan, blood draw, clinical assessment, neuropsychological assessments, eye testing, study partner interview and an optional lumbar puncture.

For further information, please call Daniela Mora-Fisher, Clinical Research Study Assistant at 416 603 5800 ext. 5914 or email daniela.mora-fisher@uhn.ca.

CIHR-FTLD: Multimodal Assessment for Predicting Pathological Substrate in Frontotemporal Lobar Degeneration

This is an observational study which aims to establish diagnostic tools in order to make an accurate ante-mortem clinical and pathological diagnosis of patients with clinical FTLD syndromes. Eligible participants and their caregivers are asked to come in for one study visit, which usually takes 2-3 full days during which the following assessments are performed: MRI scan, PET scan, blood draw, clinical assessment, neuropsychological testing, study partner interview and an optional lumbar puncture.

For further information, please call Daniela Mora-Fisher, Clinical Research Study Assistant at 416 603 5800 ext. 5914 or email daniela.mora-fisher@uhn.ca.

FOXY: A Phase 2 Clinical Trial of Intranasal Oxytocin for Frontotemporal Dementia

This is a double blind, placebo-controlled study which aims to test the hypothesis that intranasal oxytocin will reduce social apathy and empathy deficits as compared with placebo in patients with Frontotemporal Dementia (FTD). Three dose schedules of intranasal oxytocin (low, medium and high) will be tested on eligible participants. Patients and their caregivers will be asked to come in for a 1-day screening visit during which the following tests will be done: 12-lead electrocardiogram (ECG), blood draw, clinical assessments, neuropsychological testing and MRI (if no previous MRI scans are available). Upon successful screening, the participant and the study partner will be asked to come back for 4 more study visits (Baseline 1, End of Treatment 1, Baseline 2 and End of Treatment 2). Each of these study visits will take 1 day to complete and will involve the following common assessments: ECG, blood draw, clinical assessments and neuropsychological testing. The entire study will take approximately 22 weeks to complete.

For further information, please call Daniela Mora-Fisher, Clinical Research Study Assistant at 416 603 5800 ext. 5914 or email daniela.mora-fisher@uhn.ca.

ALLFTD: ARTFL LEFFTDS Longitudinal Frontotemporal Dementia Study

This is a 5-year observational study which aims to evaluate sporadic and familial frontotemporal lobar degeneration (FTLD) patients and asymptomatic family members of familial FTLD patients. The study has two arms: a "longitudinal arm" involving a comprehensive assessment of clinical, functional, imaging, and biofluid data collection, and a "biofluid focused arm" involving limited clinical data to accompany biospecimen collection. The Longitudinal arm takes 2-3 days to complete all study assessments (blood draw, clinical assessments, neuropsychological testing, MRI and optional lumbar puncture) and the Biofluid arm involves 1 day to complete limited assessments (blood draw, clinical assessments, neuropsychological testing and optional lumbar puncture). Participants in the Longitudinal arm will be asked to come back every year for 5 years to complete the same assessments while participants in the Biofluid arm will be followed up remotely by phone interview and online surveys. A reliable study partner who can report on the participant's recent behaviour, cognitive and functional abilities will have to be available in order to be eligible for the study.

For further information, please call Daniela Mora-Fisher, Clinical Research Study Assistant at 416 603 5800 ext. 5914 or email daniela.mora-fisher@uhn.ca.

Empathy Study: A pilot study assessing the benefits of a dementia caregiver educational brochure on decreased empathy and emotion recognition in patients with neurodegenerative disease

This study is investigating the use of an educational booklet about emotion recognition changes in people with cognitive impairment, dementia, and neurodegenerative disease and is primarily measuring caregiver mood, emotions, and burden. The study involves a ~2-hour appointment at Toronto Western Hospital and you will be compensated $25 for this study visit to cover transportation/parking. There will be a task where both the caregiver and the patient (separately) guess the emotions of the people in a video, questionnaires for the caregiver, and time to read through the educational booklet and to evaluate it. One month from the appointment, we will call the caregiver again and complete some of the questionnaires over the phone (~20 min).

For further information, please call Daniela Mora-Fisher, Clinical Research Study Assistant at 416 603 5800 ext. 5914 or email daniela.mora-fisher@uhn.ca and specify Empathy Study.

Oculomotor Function Testing in Patients Who Suffered Concussion

This study is investigating the use self-paced saccades (and other oculomotor measures) in patients with acute concussion as a biomarker for detection and examine the change in self-paced saccades (and other oculomotor measures) over 6 months in patients who suffered a concussion (compared to controls).

Patients will be given questionnaires (10 minutes) and have oculomotor function testing (30 minutes) at baseline (i.e., within 7 days of concussion) and 3 follow-up visits (i.e., 1, 3, and 6 months after concussion).

For information, please contact Mozhgan Khodadadi at 416 603 5800 ext. 4025 or email mozhgan.khodadadi@uhn.ca.

Post-Concussion Syndrome in Professional Athletes: A Multidisciplinary Study

The purpose of this research is to examine the relationship between repeated concussions and late decline of brain function. For this research study, we are asking athletes some of whom suffer from the after-effects of repeated concussions to undergo a series of clinical, imaging and blood tests outlined below in order to examine the effects of repeated concussions on brain function and brain structure. In addition, all participants agreeing to participate in the study will be asked to will their brains to The Krembil Brain Institute Concussion Project at the Toronto Western Hospital with the consent and full knowledge of their families and doctors. However, it is possible to participate in the research without agreeing to a brain donation.

For information, please contact Mozhgan Khodadadi at 416 603 5800 ext. 4025 or email mozhgan.khodadadi@uhn.ca.

ANAVEX2-73 Study

This is a double-blind, randomized, placebo-controlled study. This clinical trial will investigate the safety and potential efficacy (whether a drug works) of ANAVEX2-73 in patients aged 60 to 85 years of age with early Alzheimer's disease. The drug has shown in research studies that it may improve mental activities that are involved in learning, remembering and using general daily knowledge. It may protect brain neurons (brain nerve cells) that are usually damaged in Alzheimer's disease. It is thought that ANAVEX2-73 acts by attaching to and activating specific proteins called "survival receptors". This may enable ANAVEX2-73 to modify AD. This study will involve participation for approximately 52 weeks.

For further information, please call 416 603 5910 or email bghazanf@uhnresearch.ca.

CCNA: The Canadian Consortium on Neurodegeneration in Aging

Observation study of people with various types of dementia and/or cognitive complaints between the ages of 50-90. This study aims at determining who is at risk of developing dementia, which tests are most effective at detecting dementia, and helping with the understanding and diagnosis of the following forms of dementia: Mild Cognitive Impairment, Alzheimer's disease, Frontotemporal Dementia, Lewy Body Dementia, Parkinson's Disease, as well as healthy controls. Study collects clinical, neuropsychological, and MRI imaging data from study participants.

For further information, please call 416 603 5910 or email bghazanf@uhnresearch.ca.

BEAM: Brain-Eye Amyloid Memory Study

Observation study to investigate how effective non-invasive eye measurements are at identifying participants aged 50-90 with various types of dementias including: Mild Cognitive Impairment, Alzheimer's Disease, Vascular Cognitive Impairment, Parkinson's Disease, Lewy Body Disease, and healthy controls. Study collects clinical, neuropsychological, MRI imaging data, PET imaging data, eye-tracking data, and ocular measurements.

For further information, please call 416 603 5910 or email bghazanf@uhnresearch.ca.​