Impact of microglial activation on synaptic density in Alzheimer’s disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

29 Nov 2024 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Cofinancement institut Roche et ANR (Agence Nationale pour la Recherche)

External identifiers

EU CT number

2024-516566-11-00

EudraCT number

2023-000124-11

ClinicalTrials.gov

NCT05911178

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Analyze, in vivo, the interplay between microglial activation and tau pathology in Alzheimer disease (AD) using respectively [18F]-DPA-714 and [18F]-Ro948 tracers by Position Emission Tomography (PET), and their consequences on synaptic density using [11C]-UCB-J, a recent PET radioligand.

Secondary objectives 10

1. Longitudinal analysis: Evaluation of the regional alteration of the binding of each radiotracer between the baseline and the 2-year follow up imaging.
2. To study the role that global and regional tau deposition plays on the rapidity of AD progression, after one and two-year period of follow up
3. To study the impact of global and regional synaptic density on the rapidity of AD progression after one and two-year period of follow up.
4. To assess peripheral and CSF immune biomarkers by broad spectrum immunophenotyping and/or functional studies
5. To compare central and systemic inflammation, tau load and synaptic density between early and late onset sporadic AD
6. To determine clinical, biological and imaging markers of prognosis on disease evolution over 2 years follow up.
7. To analyze the correlations between clinical/cognitive assessment and molecular PET imaging.
8. To analyze the correlations between clinical and neuropsychological data and the profile of regional atrophy and others MRI markers.
9. To analyze the role of ApoE genotypes of molecular imaging and the profile of AD progression.
10. To assess atrophy of the nucleus basalis of Meynert and locus coeruleus and its relation with cognition at baseline and after 2 years of follow-up.

Conditions and MedDRA coding

Alzeihmer disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. General inclusion criteria: Adult (men or women), Women old enough to procreate under effective contraception, signed consent, for the patients absence of general or systemic disorders that may interfere with cognition.
2. IFor the controls: absence of subjective problems with memory and normal scores on the MMSE (MMSE > 27) with no more than one word missing, older than 50 years old, scores on the Free and Cued Selective Reminding Test (FCSRT) of >25 for free recall and >44 for total recall, absence of general or systemic disorders that may interfere with cognition at follow-up.
3. For patients with Alzheimer’s Disease at the early stage: AD patients will be defined as EOAD or LOAD according to the age of the onset of the disease as EOAD: onset of the disease ≤ 65 years and LOAD: onset of the disease > 65 years.
4. Progressive amnestic syndrome, associated or not with other cognitive impairments or predominant parietal cognitive, CDR = 0.5 or 1 syndrome (parietal phenotype of AD) for EOAD,
5. Absence of general or systemic disorders that may interfere with cognition or PET imaging analysis,
6. Absence of brain lesions as determined by MRI carried out within the framework of usual care.
7. Presence of CSF biomarkers profile suggestive of AD

Exclusion criteria 8

1. Subject with a psychiatric evolutionary and/or badly checked pathology (left to the judgement of the investigator).
2. Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
3. Current auto-immune disease, subject presenting contraindications to the 3T MRI
4. Known or supposed histories (≤5 years) of severe alcoholism or misuse of drugs
5. Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on the criteria of diagnosis.
6. No health insurance, pregnant, breast-feeding woman or planning a pregnancy in two years of follow-up.
7. Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders.
8. Person placed under the protection of justice, patient under guardianship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The degree of correlation at baseline between [18F]-DPA-714, [18F]-Ro948, and [11C]-UCB-J expressed in SUVr will be assessed with Kendall's Tau test

Secondary endpoints 1

1. The multivariate approach of the Mixed Model Repeated Measures (MMRM) will be used to evaluate the longitudinal evolution of clinical and instrumental parameters collected. Analyses will be adjusted for clinical and demographic characteristics at baseline.

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Sponsor organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Address

1 Rue Cabanis

City

Paris

Postcode

75014

Country

France

Scientific contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Khaoussou SYLLA

Public contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Khaoussou SYLLA

Locations

1 EU/EEA country · 3 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 10 files

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

Application history

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