Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk

NCT07007208 | Not Yet Recruiting Phase 2

• 2 other identifiers: RC31/23/03712023-507668-38-00
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) is characterized by a long-lasting silent phase. Among initial events, emergence of tau pathology in locus coeruleus (LC) brainstem nucleus, well before the one observed in medial temporal cortex, is highly relevant. LC integrity and function can be assessed in vivo with MRI and pupil measures. The current research proposes to evaluate these LC markers in an aged healthy cohort (n=100, with half APOE4 positive) and to relate these markers with cerebral tau pathology, AD risk and cognitive function.

Conditions

Alzheimer Disease

Keywords

PET; MRI; occulometry; locus coeruleus; Alzheimer disease

Outcome Measures

Primary Outcomes (1)

• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam

  The diagnostic capabilities (sensitivity, specificity and AUC) of each of the elements of oculometry (pupillary response, number, latency and amplitude of ocular saccades), functional MRI (LC-hippocampus and LC-prefrontal cortex) and structural MRI (LC intensity) for a positive PET-Tau examination

  24 monnths

Secondary Outcomes (16)

• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4- groups

  24 months

• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4+ groups

  24 months

• The relationship between different LC biomarkers

  24 months

• The link between PET Tau uptake in pupillometry

  24 months

• The link between PET Tau uptake in oculometry

  24 months

Study Arms (1)

experimental arm

EXPERIMENTAL

TEP exam, MRI exam, oculometry assessment and cognitive tasks

Drug: a positon emission tomography (PET) exam; Other: MRI Contrast; Other: oculometry assessment; Other: cognitive exams

Interventions

a positon emission tomography (PET) exam DRUG

TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)

experimental arm

MRI Contrast OTHER

Data acquisition will include different sequences (anatomical MRI, resting fMRI). The MRI sequences performed will be anatomical imaging (i.e. T1 imaging, FLAIR), a diffusion sequence, a neuromelanin-sensitive sequence and functional imaging at rest (i.e. "the resting state", which allows the functional connectivity within the so-called "default" network to be assessed).

experimental arm

oculometry assessment OTHER

Pupillometry and oculometry will be conducted using an EyeBrain medical device (class IIa). Several cognitive tasks will be submitted to the participant, during which the same measurements will be taken. Different stimuli will be presented on the computer screen (visual scenes, text, geometric shapes) during the eye tracking measurement, and an instruction (cognitive task, such as semantic categorization, free exploration of the gaze, reading, saccade execution) will be associated with each type of stimulus. The successive stimuli will be spaced more than 7 secondes apart in order to allow the pupillary response to the first stimulus to be recorded and then to return to the basal diameter before presentation of the next stimulus.

experimental arm

cognitive exams OTHER

Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.

experimental arm

Eligibility Criteria

• Age: 60 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant in the INSPIRE-T cohort
• Normal cognitive assessment
• MMSE score ≥ 27 out of 30 (Mini-Mental State Examination)
• Normal visual abilities (in corrected or uncorrected vision)
• Normal motor skills

You may not qualify if:

• Subjects with a contraindication to MRI exam
• Subjects with a known allergic reaction to the PET radiopharmaceutical (\[18F\] Flortaucipir) or any of its excipients
• Subjects with an ophthalmological pathology making oculometric measurements difficult
• Subjects with neurological or psychiatric pathologies

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

University Hospital of Toulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

PAYOUX P Pierre, MD

CONTACT

+33 (0)562746169; payoux.p@chu-toulouse.fr

DELRIEU J Julien, MD

CONTACT

+33 (0)5 61 77 70 58; dlerieu.j@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single group with ApoE4 carriers (n=50) and non-ApoE4 carriers (n=50)

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: June 5, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2029
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)