Tau and Amyloid PET imaging in normal aging, early Alzheimer's disease and related syndroms.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cliniques Universitaires Saint-Luc

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Diseases [C] - Nervous System Diseases [C10]

Trial duration

20 May 2019 → ongoing

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

FNRS

External identifiers

EU CT number

2024-517074-17-00

EudraCT number

2018-003473-94

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Evaluate the regional deposition of p-TAU protein aggregates using F18-MK6240 PET/CT, non-invasive in vivo imaging within the brain of patients affected by several neurodegenerative disorders. Patients’ data (MCI, mild AD, non-AD dementia) will be compared to a control group data.

Secondary objectives 9

1. To evaluate how tau PET signal distinguish patients with AD, patients with non-AD syndrome, and controls
2. To evaluate how tau PET signal depends on age, and on genetic risks in non-demented controls
3. To compare tau PET imaging to tau measures in the cerebrospinal fluid (CSF)
4. To evaluate how tau PET imaging can predict progression to dementia in MCI and control participants
5. To evaluate how tau PET signals relate to (functional) MRI data
6. To evaluate how tau PET signals relate to blood-derived biomarkers
7. To evaluate how tau PET signals relate to cognitive performance
8. To evaluate how tau PET signals relate to electroencephalographic (EEG) signals
9. To evaluate how to tau PET measures evolve over time, in relation to cognitive performance and the other biomarkers

Conditions and MedDRA coding

Alzheimer's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Patients with MCI due to AD or mild AD : Age at least 45 years
2. Able to read and write in French, with a minimum 5 years of formal education
3. Attended the Memory Clinic of Cliniques Universitaires Saint-Luc
4. Are able to consent and willing to participate in the study
5. 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.
6. Have a study partner or can identify someone willing in principle to be a study partner
7. 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.
8. Patients with non-AD syndrome : Age at least 20 years
9. Able to read and write in French, with a minimum 5 years of formal education
10. 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
11. Are able to consent and willing to participate in the study
12. 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
13. Have a study partner or can identify someone willing in principle to be a study partner
14. Non-demented controls : Age at least 20 years
15. Able to read and write in French; minimum 5 years of formal education
16. Recruited among caregivers of patients attending the Memory Clinics, through advertisement, or among patients attending the Memory Clinics but with normal neuropsychological exam.
17. Are able to consent and willing to participate in the study
18. Have normal cognition as defined by an MMSE ≥ 26/30 (25/30 if education lower than high school).
19. 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.

Exclusion criteria 8

1. 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.
2. 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)
3. 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.
4. Any contraindications for MRI or PET scan
5. 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.
6. 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.
7. 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).
8. Pregnancy, or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. F18-MK6240 regional SUVr or spatial extension measure differences between patients and controls

Secondary endpoints 5

1. 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.
2. Associations between F18-MK6240 regional SUVr or spatial extension measures and CSF biomarker outcomes - Aβ, t-tau, p-tau
3. Associations between F18-MK6240 regional SUVr or spatial extension measures and Amyloid-PET imaging - Global and regional distribution of amyloid deposition
4. 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
5. Associations between F18-MK6240 regional SUVr or spatial extension measures and Blood-derived biomarkers - Amyloid oligomers - Phosphorylated and non-phosphorylated tau species

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cliniques Universitaires Saint-Luc

Sponsor organisation

Cliniques Universitaires Saint-Luc

Address

Hippokrateslaan 10, Batiment 54 Batiment 54

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Bernard Hanseeuw

Public contact point

Organisation

Cliniques Universitaires Saint-Luc

Contact name

Bernard Hanseeuw

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications