FLORQUINITAU (18F) for Alzheimer's disease

Inclusion criteria

• {"criterion_text":"- Patients with MCI due to AD or mild AD : Age at least 45 years\n- Attended the Memory Clinic, the Stroke Clinic (CAA), the Neuromuscular Clinic (ALS), or the Movement Disorder (PSP/CBD/LBD) Clinic of Cliniques Universitaires Saint-Luc\n- Are able to consent and willing to participate in the study\n- Are clinically suspected to suffer: - from cerebral amyloid angiopathy (CAA), Fronto-temporal Lobar Degeneration, Progressive Supranuclear Palsy, Corticobasal Degeneration, Lewy body disease, or Amyotrophic Lateral Sclerosis by a clinical neurologist. - from MCI due to AD or mild AD dementia but have either a negative amyloid-PET scan OR a normal measure of Aβ-42 in the CSF\n- Have a study partner or can identify someone willing in principle to be a study partner\n- Non-demented controls : Age at least 20 years\n- Able to read and write in French; minimum 5 years of formal education\n- Recruited among caregivers of patients attending the Memory Clinics, through advertisement, or among patients attending the Memory Clinics but with normal neuropsychological exam.\n- Are able to consent and willing to participate in the study\n- Have normal cognition as defined by an MMSE ≥ 26/30 (25/30 if education lower than high school).\n- Have an available amyloid-PET scan OR an available CSF measure of Aβ-42 conducted for clinical reasons OR in another research study OR are willing to undertake an amyloid-PET scan for the present study OR are willing to undertake a CSF measure of Aβ-42 for the present study.\n- Able to read and write in French, with a minimum 5 years of formal education\n- Attended the Memory Clinic of Cliniques Universitaires Saint-Luc\n- Are able to consent and willing to participate in the study\n- Are diagnosed either with mild cognitive impairment (MMSE ≥ 24/30) using the Petersen criteria (2004) or with mild AD dementia (MMSE ≥ 20/30) using the McKhann criteria (2011) by a clinical neurologist.\n- Have a study partner or can identify someone willing in principle to be a study partner\n- Have either a positive amyloid-PET scan OR an abnormal measure of Aβ-42 in the CSF OR an abnormal ratio between total tau and Aβ-42 in the CSF.\n- Patients with non-AD syndrome : Age at least 20 years"}

Exclusion criteria

• {"criterion_text":"- Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington’s disease, multiple sclerosis, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder.\n- Any cancer or history of cancer in the preceding 2 years (excluding cutaneous basal or squamous cell cancer resolved by excision and localized prostate cancer in male subjects)\n- Any current medical conditions that are clinically significant and might make the subject’s participation in an investigational trial unsafe, e.g., uncontrolled or unstable disease of any major organ system; history within the last 3 months of any acute illness of a major organ system requiring emergency care or hospitalization, including re-vascularization procedures; severe renal or hepatic failure; unstable or poorly controlled diabetes mellitus, hypertension, or heart failure; any clinically relevant abnormalities in blood parameters in routine assessments; severe loss of vision, hearing or communicative ability; or any conditions preventing co-operation or completion of the required assessments in the trial, as judged by the investigator.\n- Any contraindications for MRI or PET scan\n- Any evidence of intracranial pathology which, in the opinion of the Investigator, may affect cognition, including but not limited to brain tumors (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), recent hemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Participants with a MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.\n- Participation in a clinical trial of an investigational product (IMP) in the 30 days preceding the screening visit. Entering a clinical trial of an investigational product (IMP) is allowed during the current study once the baseline examinations have been performed. The follow-up examinations scheduled in the current study will be proposed to the participants who will have entered a clinical trial during their participation in the current study, depending on the examinations that are scheduled in the clinical trial.\n- Women of child-bearing potential (WOCBP1, non-menopausal), younger than 55 years old, following any method of contraception not recommended by the Clinical Trial Facilitation Group (CTFG). The use of a highly effective contraception measure should indeed be maintained during any F18 radio-labelled pharmaceutical exposure, until complete F18 decay (meaning at least a minimum period of 18-24 hours after injection).\n- Pregnancy, or breastfeeding"}

Primary endpoints

• {"endpoint_text":"- F18-MK6240 regional SUVr or spatial extension measure differences between patients and controls","definition_or_measurement_approach":"Regional SUVr or spatial extension measures obtained with F18-MK6240 PET/CT to compare patients and controls."}

Secondary endpoints

• {"endpoint_text":"- Associations between F18-MK6240 regional SUVr or spatial extension measures and: Cognitive outcomes - Global cognitive measures - Verbal Episodic Memory - Visuospatial/Constructional - Language - Attention/Executive Functioning - Spatial navigational skills; - Face perception and recognition abilities; Specific semantic memory measures; - Short-term memory binding abilities; - Specific episodic memory processes; - Implicit learning abilities.","definition_or_measurement_approach":"Associations between regional SUVr/spatial extension PET measures with a range of cognitive outcome measures (global and domain-specific cognitive tests)."}
• {"endpoint_text":"- Associations between F18-MK6240 regional SUVr or spatial extension measures and CSF biomarker outcomes - Aβ, t-tau, p-tau","definition_or_measurement_approach":"Associations between PET regional SUVr/spatial extension measures and cerebrospinal fluid biomarkers (Aβ, total tau, phosphorylated tau)."}
• {"endpoint_text":"- Associations between F18-MK6240 regional SUVr or spatial extension measures and Amyloid-PET imaging - Global and regional distribution of amyloid deposition","definition_or_measurement_approach":"Associations between PET regional SUVr/spatial extension measures and amyloid-PET imaging measures (global and regional amyloid distribution)."}
• {"endpoint_text":"- Associations between F18-MK6240 regional SUVr or spatial extension measures and Neuroimaging outcomes (MRI) - Regional and whole brain volume - Regional cortical thickness - Resting-state functional connectivity - Diffusion-weighted imaging - Task-related brain activity","definition_or_measurement_approach":"Associations between PET regional SUVr/spatial extension measures and multiple MRI-derived neuroimaging outcomes (volumes, cortical thickness, functional connectivity, DWI, task-related activity)."}
• {"endpoint_text":"- Associations between F18-MK6240 regional SUVr or spatial extension measures and Blood-derived biomarkers - Amyloid oligomers - Phosphorylated and non-phosphorylated tau species","definition_or_measurement_approach":"Associations between PET regional SUVr/spatial extension measures and blood-derived biomarkers (amyloid oligomers, phosphorylated and non-phosphorylated tau species)."}

Methods

• Recruited among caregivers of patients attending the Memory Clinics
• Through advertisement
• Among patients attending the Memory Clinics (Memory Clinic, Stroke Clinic (CAA), Neuromuscular Clinic (ALS), Movement Disorder Clinic (PSP/CBD/LBD) of Cliniques Universitaires Saint-Luc)
• Participants may be recruited if they have prior amyloid-PET or CSF measures or be willing to undertake these for the study

Belgium

Earliest CTIS Part Ii Submission Date

06-08-2024

Latest Decision Or Authorization Date

09-10-2024

Processing Time Days

64

Number Of Sites

1

Number Of Participants

500

Primary sponsor

Full Name

Cliniques Universitaires Saint-Luc

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium