Alzheimer DiseasePhase 2Locus-TauNCT07007208
Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk
A Phase 2 study testing a positon emission tomography (PET) exam, MRI Contrast and oculometry assessment in people with Alzheimer Disease, run by University Hospital, Toulouse at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- a positon emission tomography (PET) exam, MRI Contrast and oculometry assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 2 Feb 2026to 31 Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 a neurodegenerative condition or a history of cerebral ischemia
- Subjects with a psychiatric disorder and a PHQ-9 score > 10 or under treatment with NRI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
University Hospital of Toulouse
Toulouse, 31059
Payoux Pierre, MD, +33 (0)5 62 74 61 69, payoux.p@chu-toulouse.fr
Delrieu Julien, MD, +33 (0)5 61 77 70 58, delrieu.j@chu-toulouse.fr
About this study
Official title: Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk.
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.
Read the detailed description
Early tau pathology in the LC may induce dysfunction of the LC-NA system, contribute to initial cognitive decline and possibly be predictive of future AD occurrence. 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, 2) 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, and 3) to study the link between LC biomarkers and cognitive performance.
To complete these objectives, the project will evaluate, in healthy older volunteers from the INSPIRE-T cohort (n=100, > 60 years old), biomarkers of LC neuronal integrity, LC-forebrain connectivity, and LC tonic and phasic activity. Additionally, a positon emission tomography (PET) exam will be conducted using tau-specific tracer. Detailed cognitive assessment will also be performed, including assessment of a priori NA-dependent and NA-independent cognitive functions. In the studied cohort (n = 100), half volunteers will be recruited based on genetic AD risk (APOE4 positive) and the other half based on the absence of risk (APOE4 negative).
- Conditions
- Alzheimer Disease
- Being tested
- a positon emission tomography (PET) exam, MRI Contrast, oculometry assessment, cognitive exams
- Keywords
- PET, MRI, occulometry, locus coeruleus, Alzheimer disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
a positon emission tomography (PET) examDrug
TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)
MRI ContrastOther
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).
oculometry assessmentOther
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.
cognitive examsOther
Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.
| Study group | Role | What they receive |
|---|---|---|
| experimental arm | Experimental | TEP exam, MRI exam, oculometry assessment and cognitive tasks Receives: Drug: a positon emission tomography (PET) exam; Other: MRI Contrast; Other: oculometry assessment; Other: cognitive exams |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 monnths
Secondary outcomes (16)
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4- groups
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 in APOe4- patients
Measured: 24 months
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4+ groups
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 in APOe4+ patients
Measured: 24 months
The relationship between different LC biomarkers
this will be evaluated by correlation and regression. The correlations will be performed both together and separately in the APOe4 status. The impact will be assessed by linear and logistic regression and will also take into account age, gender, and education level.
Measured: 24 months
The link between PET Tau uptake and PET-estimated perfusion changes
this will be assessed by the correlation between variations expressed in absolute value or as a proportion of the baseline value and Tau marking, and by regression at 12 and 24 months. The correlations will be performed both together and separately in the APOe4 status, and the regression will also take into account age, gender, and education level.
Measured: 24 months
The link between PET Tau uptake in oculometry
this will be assessed by the correlation between variations expressed in absolute value or as a proportion of the baseline value and Tau marking, and by regression. The correlations will be performed both together and separately in the APOe4 status, and the regression will also take into account age, gender, and education level.
Measured: 24 months
The link between PET Tau uptake in the structural (neuromelanin) and functional integrity of the LC by MRI
this will be assessed by correlating variations expressed as absolute values or as a proportion of the baseline value with PET Tau, and by regression at 12 and 24 months.
Measured: 24 months
The link between variations in pupillometry
this will be assessed by the correlation between variations expressed in absolute value or as a proportion of the baseline value, and by regression at 12 and 24 months.. The correlations will be performed both together and separately in the APOe4 carrier and non-carrier groups, and the regression will also take into account age, gender, and education level.
Measured: 24 months
The link between variations in occulometry
this will be assessed by the correlation between variations expressed in absolute value or as a proportion of the baseline value, and by regression at 12 and 24 months. The correlations will be performed both together and separately in the APOe4 carrier and non-carrier groups, and the regression will also take into account age, gender, and education level, at 12 and 24 months
Measured: 24 months
The link between variations in the structural (neuromelanin) and functional integrity of the LC by MRI
this will be evaluated by correlation between variations expressed as absolute values or as a proportion of the baseline value and by regression at 12 and 24 months
Measured: 24 months
The relationship between the various LC biomarkers (PET, MRI, pupillometry) and participants' cognitive performance
this 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.
Measured: 24 months
comparison between APOe4+ and APOe4-: Structural (neuromelanin) and functional integrity of the LC by MRI
this Will be assessed both at inclusion, at 12 months, and at 24 months, through regressions that will take into account age, gender, and education level.
Measured: 24 months
comparison between APOe4+ and APOe4: Cognitive performance
this Will be assessed both at inclusion, at 12 months, and at 24 months, through regressions that will take into account age, gender, and education level.
Measured: 24 months
comparison between APOe4+ and APOe4-: Pupillometry and oculometry
this Will be assessed both at inclusion, at 12 months, and at 24 months, through regressions that will take into account age, gender, and education level.
Measured: 24 months
The reliability of the amplitude of the phasic pupil response during completion of cognitive tasks
This will be validated by intraclass correlation between baseline value and value at one month (test-retest) in a subgroup of 30 participants.
Measured: 24 months
The reliability of the latency of saccadic eye movements during completion of cognitive tasks
This will be validated by intraclass correlation between baseline value and value at one month (test-retest) in a subgroup of 30 participants.
Measured: 24 months
The reliability of the amplitude of saccadic eye movements during completion of cognitive tasks
This will be validated by intraclass correlation between baseline value and value at one month (test-retest) in a subgroup of 30 participants.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2025
- Study start2 Feb 2026
- Primary completion31 Jan 2029 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single group with ApoE4 carriers (n=50) and non-ApoE4 carriers (n=50)
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07007208
- Sponsor's protocol ID
- RC31/23/0371
- Other IDs
- 2023-507668-38-00, 2023
- Acronym
- Locus-Tau
- Status last verified
- Jul 2026
- First submitted
- 12 May 2025
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk.
- ClinicalTrials.gov ID
- NCT07007208
- Acronym / sponsor ID
- Locus-Tau / RC31/23/0371
- Conditions
- Alzheimer Disease
- Keywords
- PET, MRI, occulometry, locus coeruleus, Alzheimer disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 31 Jan 2029 (estimated)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 5 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Early tau pathology in the LC may induce dysfunction of the LC-NA system, contribute to initial cognitive decline and possibly be predictive of future AD occurrence. 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, 2) 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, and 3) to study the link between LC biomarkers and cognitive performance.
To complete these objectives, the project will evaluate, in healthy older volunteers from the INSPIRE-T cohort (n=100, > 60 years old), biomarkers of LC neuronal integrity, LC-forebrain connectivity, and LC tonic and phasic activity. Additionally, a positon emission tomography (PET) exam will be conducted using tau-specific tracer. Detailed cognitive assessment will also be performed, including assessment of a priori NA-dependent and NA-independent cognitive functions. In the studied cohort (n = 100), half volunteers will be recruited based on genetic AD risk (APOE4 positive) and the other half based on the absence of risk (APOE4 negative).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single group with ApoE4 carriers (n=50) and non-ApoE4 carriers (n=50)
| Arm | Type | Receives |
|---|---|---|
| experimental arm | Experimental | Drug: a positon emission tomography (PET) exam, Other: MRI Contrast, Other: oculometry assessment, Other: cognitive examsTEP exam, MRI exam, oculometry assessment and cognitive tasks |
Who may qualify
- Ages
- 60 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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 a neurodegenerative condition or a history of cerebral ischemia
- Subjects with a psychiatric disorder and a PHQ-9 score > 10 or under treatment with NRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| a positon emission tomography (PET) examTEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq) | Drug | experimental arm |
| MRI ContrastData 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). | Other | experimental arm |
| oculometry assessmentPupillometry 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. | Other | experimental arm |
| cognitive examsCognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare. | Other | experimental arm |
Primary outcome
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam
Time frame: 24 monnths
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
16 secondary outcomes
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4- groups
Time frame: 24 months
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4+ groups
Time frame: 24 months
The relationship between different LC biomarkers
Time frame: 24 months
The link between PET Tau uptake and PET-estimated perfusion changes
Time frame: 24 months
The link between PET Tau uptake in oculometry
Time frame: 24 months
The link between PET Tau uptake in the structural (neuromelanin) and functional integrity of the LC by MRI
Time frame: 24 months
The link between variations in pupillometry
Time frame: 24 months
The link between variations in occulometry
Time frame: 24 months
The link between variations in the structural (neuromelanin) and functional integrity of the LC by MRI
Time frame: 24 months
The relationship between the various LC biomarkers (PET, MRI, pupillometry) and participants' cognitive performance
Time frame: 24 months
comparison between APOe4+ and APOe4-: Structural (neuromelanin) and functional integrity of the LC by MRI
Time frame: 24 months
comparison between APOe4+ and APOe4: Cognitive performance
Time frame: 24 months
comparison between APOe4+ and APOe4-: Pupillometry and oculometry
Time frame: 24 months
The reliability of the amplitude of the phasic pupil response during completion of cognitive tasks
Time frame: 24 months
The reliability of the latency of saccadic eye movements during completion of cognitive tasks
Time frame: 24 months
The reliability of the amplitude of saccadic eye movements during completion of cognitive tasks
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing a positon emission tomography (PET) exam, MRI Contrast and oculometry assessment in people with Alzheimer Disease, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact PAYOUX P Pierre, MD (+33 (0)562746169, payoux.p@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam (time frame: 24 monnths). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.