Biomarkers of the locus coeruleus nucleus: links with early tau pathology, cognition and AD risk. LocusTau

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Feb 2026 → ongoing

Decision date (initial)

2024-11-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fondation Vaincre Alzheimer.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

The present project has the following objectives: 1) to relate different biomarkers of LC function measured in vivo with AD risk and future AD occurrence, in order to evaluate their relevance for earliest AD diagnosis,

Secondary objectives 2

1. to investigate how LC biomarkers can account for underlying brain tau pathology in asymptomatic older individuals;a related objective will be to validate LC biomarkers as reliable proxies of tau pathology occurrence,
2. to study the link between LC biomarkers and cognitive performance.

Conditions and MedDRA coding

Alzheimer’s Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. - Age ≥ 60 years.
2. - Participant in the INSPIRE-T cohort.
3. - Normal cognitive assessment.
4. - MMSE score ≥ 27 out of 30 (Mini-Mental State Examination).
5. - Normal visual abilities (in corrected or uncorrected vision).
6. - Normal motor skills.
7. - Free, informed and written consent signed by the participant and the investigator (no later than the day of inclusion and before any examination required by the research).
8. - Person affiliated to or benefiting from a social security scheme.
9. For participants in the ApoE4 group only: presence of the ApoE4 allele (phenotyping of ApoE protein isoforms carried out as part of the INSPIRE project).

Exclusion criteria 6

1. - Subjects with a contraindication to MRI exam
2. - Subjects with a known allergic reaction to the PET radiopharmaceutical ([18F] Flortaucipir) or any of its excipients
3. - Subjects with an ophthalmological pathology making oculometric measurements difficult (glaucoma, age-related macular degeneration, non-operated cataracts).
4. - Persons protected by law (adults under guardianship or safeguard of justice).
5. Subjects participating in another research protocol and under exclusion delay.
6. Subjects with neurological or psychiatric pathology.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. diagnostic capabilities (sensitivity, specificity and AUC) 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 exam.

Secondary endpoints 7

1. 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 will be evaluated separately for the APOe4- and APOe4+ groups
2. The relationship between different LC biomarkers (PET, MRI, pupillometry).
3. The reliability of pupillometry and oculometry measurements will be validated by retesting a subgroup of 30 participants 1 to 4 weeks apart.
4. The link between PET Tau uptake and changes at 12 and 24 months in pupillometry, oculometry and the structural (neuromelanin) and functional integrity of the LC measured on MRI will be assessed by correlating variations expressed as absolute values or as a proportion of the baseline value with PET Tau, and by regression.
5. The link between variations in pupillometry, oculometry and the structural (neuromelanin) and functional integrity of the LC measured on MRI at 12 and 24 months will be evaluated by correlation between variations expressed as absolute values or as a proportion of the baseline value and by regression
6. The relationship between the various LC biomarkers (PET, MRI, pupillometry) and participants' cognitive performance will be assessed both at inclusion and at 12 and 24 months, using regressions that take into account age, gender, level of education and APOe4 status.
7. All items will be compared between APOe4+ and APOe4- groups.a) Structural (neuromelanin) and functional integrity of the LC measured by MRI. b) Cognitive performance. c) Pupillometry and oculometry. d) And their evolution at 12 and 24 months.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Pierre Payoux

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Pierre Payoux

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