Alzheimer DiseaseLEADNCT04403165
Locus-coeruleus Function in Normal Elderly and AD Risk
A study testing Nocturnal polysomnography (NPSG), Lumbar Puncture (LP) and PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB) in people with Alzheimer Disease, run by NYU Langone Health at 2 sites in United States.
Trial summary
Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Nocturnal polysomnography (NPSG), Lumbar Puncture (LP) and PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB)
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Aug 2020to 26 Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female subjects with normal cognition and 55-75 years of age will be enrolled.
- Subjects will be within normal limits on neurological and psychiatric examinations.
- All subjects enrolled will have a CDR of 0. This will be evaluated through a clinical interview administered by a study physician (informant interview will not be required).
- All subjects will have had a minimum of 12 years of education.
Who cannot join
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, stroke, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
- Significant history of alcoholism or drug abuse.
- Significant history of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
- Geriatric Depression Scale (short form)>6.
- Insulin dependent diabetes.
- Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions.
Show all 12Show fewer
- Physical impairment of such severity as to adversely affect the validity of psychological testing.
- Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
- History of a first-degree family member with early onset (age <60 years) dementia.
- Irregular sleep-wake rhythms (based on the actigraphy recordings) or significant OSA (AHI4%≥15).
- Taking Coumadin/warfarin and/or medications affecting cognition or sleep.
- Failure to complete all study visit within 4 months
Trial locations and contacts
2 sites in 1 country.
United States2 sites
NYU Grossman School of Medicine
New York, New York, 10016
Icahn School of Medicine Mount Sinai
New York, New York, 10029
About this study
Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. We have previously demonstrated functional vulnerability of the LC to aging and stress, as well as an association between higher cerebrospinal fluid (CSF) tau and impaired sleep phenomena influenced by the LC. We now aim to test whether LC dysfunction can be measured in preclinical AD stages by LC targeted imaging, and whether it objectively affects sleep architecture and attention. We will test this hypothesis in 30 cognitively normal older adults by performing a full clinical evaluation, one night of polysomnography, a lumbar puncture to obtain cerebrospinal fluid, [11C]MRB PET-MR, and attention testing. This study has the potential to identify a new mechanism by which tau pathology contributes to sleep and attention dysfunction and may provide a new therapeutic target for AD prevention.
Read the detailed description
The purpose of this study is three-fold: to test whether lower NET availability in the LC is associated with: first, CSF tau levels typical of preclinical stages of AD (Aim 1); second, reduced REM and spindle density (Aim 2); and third, impaired performance on attention tasks (Aim 3). The goal is to test the overarching hypothesis that LC dysfunction occurs in preclinical AD stages, can be measured with MRB-PET, and translates into impairment of sleep architecture (LC tonic dysfunction) and attention (LC phasic dysfunction).
- Conditions
- Alzheimer Disease
- Being tested
- Nocturnal polysomnography (NPSG), Lumbar Puncture (LP), PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB), Psychomotor Vigilance Task (PVT)
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nocturnal polysomnography (NPSG)Procedure or surgery
Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics.
Lumbar Puncture (LP)Procedure or surgery
Lumbar puncture (LP) to measure CSF P-Tau, T-Tau and Aβ42/40 ratio.
PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB)Other
PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]O-methylreboxetine ([11C]MRB) to measure NET availability.
Psychomotor Vigilance Task (PVT)Behavioural
Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance.
| Study group | Role | What they receive |
|---|---|---|
| Cognitively Normal (CN) Older Adults | Experimental | Not described Receives: Procedure: Nocturnal polysomnography (NPSG); Procedure: Lumbar Puncture (LP); Other: PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB); Behavioral: Psychomotor Vigilance Task (PVT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values
Measured: Visit 4 (1-4 weeks after LP)
Total Rapid Eye Movement (REM) Duration (Min)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Measured: Visit 3 (1-4 weeks after Visit 2)
Percentage of Time Spent in REM Sleep
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Measured: Visit 3 (1-4 weeks after Visit 2)
REM Sleep Continuity
Reported as percentage of REM runs that are less than 5, greater than or equal to 5 and greater than or equal to 10 minutes.
Measured: Visit 3 (1-4 weeks after Visit 2)
Number of sleep spindles that occur per minute during the N2 stage of sleep (N2 Spindle Density)
N2 Spindle Density is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Measured: Visit 3 (1-4 weeks after Visit 2)
Mean Psychomotor Vigilance Test (PVT) Reaction Time
PVT measures the reaction speed to a randomly time-occuring visual stimuli, allowing the assessment of several aspects of attention including response times, attention lapses and false starts.
Measured: Visit 3 (1-4 weeks after Visit 2)
Mean picture test response time
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
Measured: Visit 3 (1-4 weeks after Visit 2)
Percentage of Correct Responses on the picture test
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
Measured: Visit 3 (1-4 weeks after Visit 2)
Secondary outcomes (1)
Levels of Hyperphosphorylated Tau (P-Tau, T-Tau)
Levels will be derived from the CSF and reported in pg/mL
Measured: Visit 4 (1-4 weeks after LP)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start6 Aug 2020
- Primary completion26 Mar 2024
- Study completion26 Mar 2024
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 NYU Langone HealthThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Ricardo Osorio, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04403165
- Sponsor's protocol ID
- 20-00002
- Other IDs
- 1R21AG067549-01
- Acronym
- LEAD
- Status last verified
- May 2026
- First submitted
- 21 May 2020
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Locus-coeruleus Function in Normal Elderly and AD Risk
- ClinicalTrials.gov ID
- NCT04403165
- Acronym / sponsor ID
- LEAD / 20-00002
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 6 Aug 2020 (actual)
- Primary completion
- 26 Mar 2024 (actual)
- Study completion
- 26 Mar 2024 (actual)
- First posted
- 27 May 2020 (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.
Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. We have previously demonstrated functional vulnerability of the LC to aging and stress, as well as an association between higher cerebrospinal fluid (CSF) tau and impaired sleep phenomena influenced by the LC. We now aim to test whether LC dysfunction can be measured in preclinical AD stages by LC targeted imaging, and whether it objectively affects sleep architecture and attention. We will test this hypothesis in 30 cognitively normal older adults by performing a full clinical evaluation, one night of polysomnography, a lumbar puncture to obtain cerebrospinal fluid, [11C]MRB PET-MR, and attention testing. This study has the potential to identify a new mechanism by which tau pathology contributes to sleep and attention dysfunction and may provide a new therapeutic target for AD prevention.
Detailed description
The purpose of this study is three-fold: to test whether lower NET availability in the LC is associated with: first, CSF tau levels typical of preclinical stages of AD (Aim 1); second, reduced REM and spindle density (Aim 2); and third, impaired performance on attention tasks (Aim 3). The goal is to test the overarching hypothesis that LC dysfunction occurs in preclinical AD stages, can be measured with MRB-PET, and translates into impairment of sleep architecture (LC tonic dysfunction) and attention (LC phasic dysfunction).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cognitively Normal (CN) Older Adults | Experimental | Procedure: Nocturnal polysomnography (NPSG), Procedure: Lumbar Puncture (LP), Other: PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB), Behavioral: Psychomotor Vigilance Task (PVT) |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female subjects with normal cognition and 55-75 years of age will be enrolled.
- Subjects will be within normal limits on neurological and psychiatric examinations.
- All subjects enrolled will have a CDR of 0. This will be evaluated through a clinical interview administered by a study physician (informant interview will not be required).
- All subjects will have had a minimum of 12 years of education.
Key exclusion criteria (12 listed)
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, stroke, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
- Significant history of alcoholism or drug abuse.
- Significant history of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
- Geriatric Depression Scale (short form)>6.
- Insulin dependent diabetes.
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 |
|---|---|---|
| Nocturnal polysomnography (NPSG)Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics. | Procedure or surgery | Cognitively Normal (CN) Older Adults |
| Lumbar Puncture (LP)Lumbar puncture (LP) to measure CSF P-Tau, T-Tau and Aβ42/40 ratio. | Procedure or surgery | Cognitively Normal (CN) Older Adults |
| PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB)PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]O-methylreboxetine ([11C]MRB) to measure NET availability. | Other | Cognitively Normal (CN) Older Adults |
| Psychomotor Vigilance Task (PVT)Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance. | Behavioural | Cognitively Normal (CN) Older Adults |
Primary outcome
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values
Time frame: Visit 4 (1-4 weeks after LP)
Total Rapid Eye Movement (REM) Duration (Min)
Time frame: Visit 3 (1-4 weeks after Visit 2)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Percentage of Time Spent in REM Sleep
Time frame: Visit 3 (1-4 weeks after Visit 2)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
REM Sleep Continuity
Time frame: Visit 3 (1-4 weeks after Visit 2)
Reported as percentage of REM runs that are less than 5, greater than or equal to 5 and greater than or equal to 10 minutes.
Number of sleep spindles that occur per minute during the N2 stage of sleep (N2 Spindle Density)
Time frame: Visit 3 (1-4 weeks after Visit 2)
N2 Spindle Density is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Mean Psychomotor Vigilance Test (PVT) Reaction Time
Time frame: Visit 3 (1-4 weeks after Visit 2)
PVT measures the reaction speed to a randomly time-occuring visual stimuli, allowing the assessment of several aspects of attention including response times, attention lapses and false starts.
Mean picture test response time
Time frame: Visit 3 (1-4 weeks after Visit 2)
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
Percentage of Correct Responses on the picture test
Time frame: Visit 3 (1-4 weeks after Visit 2)
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
1 secondary outcome
Levels of Hyperphosphorylated Tau (P-Tau, T-Tau)
Time frame: Visit 4 (1-4 weeks after LP)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
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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. This study is not recruiting at the moment.
Ricardo Osorio principal investigator
NYU Langone Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nocturnal polysomnography (NPSG), Lumbar Puncture (LP) and PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB) in people with Alzheimer Disease, run by NYU Langone Health at 2 sites in United States.
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 4 inclusion and 12 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: finished, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values (time frame: Visit 4 (1-4 weeks after LP)). The study lists 8 primary outcomes in all. 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 28 May 2026.