- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04403165
Locus-coeruleus Function in Normal Elderly and AD Risk (LEAD)
April 5, 2024 updated by: NYU Langone Health
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 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.
Study Overview
Status
Completed
Conditions
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 Type
Interventional
Enrollment (Actual)
30
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Dishari Azad
- Phone Number: 646-754-2229
- Email: Dishari.azad@nyulangone.org
Study Contact Backup
- Name: Ricardo Osorio
- Phone Number: 212-263-3255
- Email: ricardo.osorio@nyulangone.org
Study Locations
-
-
New York
-
New York, New York, United States, 10029
- Icahn School of Medicine Mount Sinai
-
New York, New York, United States, 10016
- NYU Grossman School of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
60 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cognitively Normal (CN) Older Adults
|
Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics.
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]O-methylreboxetine ([11C]MRB) to measure NET availability.
Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values
Time Frame: Visit 4 (1-4 weeks after LP)
|
Visit 4 (1-4 weeks after LP)
|
|
Total REM Duration (Min)
Time Frame: Visit 3 (1-4 weeks after Visit 2)
|
Visit 3 (1-4 weeks after Visit 2)
|
|
Percentage of Time Spent in REM Sleep
Time Frame: Visit 3 (1-4 weeks after Visit 2)
|
Visit 3 (1-4 weeks after Visit 2)
|
|
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).
|
Visit 3 (1-4 weeks after Visit 2)
|
N2 Spindle Density
Time Frame: Visit 3 (1-4 weeks after Visit 2)
|
Visit 3 (1-4 weeks after Visit 2)
|
|
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.
|
Visit 3 (1-4 weeks after Visit 2)
|
Mean Oddball Test Response Time
Time Frame: Visit 3 (1-4 weeks after Visit 2)
|
The OddBall test measures task-related attention.
Two different visual stimuli (frequent and infrequent) are presented in random succession as the subject presses a button only when the infrequent stimuli appears.
|
Visit 3 (1-4 weeks after Visit 2)
|
Percentage of Correct Responses
Time Frame: Visit 3 (1-4 weeks after Visit 2)
|
Visit 3 (1-4 weeks after Visit 2)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Levels of Hyperphosphorylated Tau (P-Tau, T-Tau)
Time Frame: Visit 4 (1-4 weeks after LP)
|
Levels will be derived from the CSF and reported in pg/mL
|
Visit 4 (1-4 weeks after LP)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Aβ42/Aβ40 Ratio
Time Frame: Visit 4 (1-4 weeks after LP)
|
The presence of amyloid plaques will be represented as the binary indicator of a CSF Aβ42/Aβ40 ratio
|
Visit 4 (1-4 weeks after LP)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Ricardo Osorio, NYU Langone Health
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 6, 2020
Primary Completion (Actual)
March 26, 2024
Study Completion (Actual)
March 26, 2024
Study Registration Dates
First Submitted
May 21, 2020
First Submitted That Met QC Criteria
May 21, 2020
First Posted (Actual)
May 27, 2020
Study Record Updates
Last Update Posted (Actual)
April 8, 2024
Last Update Submitted That Met QC Criteria
April 5, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Alzheimer Disease
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Sympathomimetics
- Vasoconstrictor Agents
- Norepinephrine
Other Study ID Numbers
- 20-00002
- 1R21AG067549-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
All of the individual participant data collected during the trial, after deidentification.
IPD Sharing Time Frame
Immediately following publication.
No end date.
IPD Sharing Access Criteria
The investigator who proposed to use the ricardo.osorio@nyulangone.org.
To gain access, data requestors will need to sign a data access agreement.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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