ElderlyNCT03053908
Orexin and Tau Pathology in Cognitively Normal Elderly
A study testing Actigraphy and Nocturnal Polysomnograpahy (NPSG) in people with Elderly and Alzheimer Disease, run by NYU Langone Health at 1 site in United States.
Trial summary
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Current consensus is that the AD pathological process begins decades before clinical symptoms occur. Read more about this study
- Who is it for?
- Ages 55 to 75 years
- Conditions the study is for
- Elderly, Alzheimer Disease
- What is being tested?
- Actigraphy and Nocturnal Polysomnograpahy (NPSG)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Mar 2018to 13 May 2019
- 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
- No healthy volunteers
- 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 both a Clinical Dementia Rating (CDR)=0 and a MMSE≥27
- All subjects will have had a minimum of 12 years of education. Among minority subjects >80% of the elderly individuals coming to the NYU-ADC meet this criterion. (The education restriction reduces performance variance on cognitive test measures and improves the sensitivity for detecting pathology and disease progression using the robust norms available at NYU. Given the majority of subjects will meet this criterion we do not consider this a major selection bias or generalization limitation for this study).
- An informed family member or life-partner (preferably bed-partner) will be interviewed over the phone or on the first or second visit to confirm the reliability of the subject interview.
Who cannot join
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders). Subjects with a Fazekas scale >2 will be excluded109.
- Significant history of alcoholism or drug abuse.
- History of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
- Geriatric Depression Scale (short form)>5.
- Insulin dependent diabetes.
- Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions (e.g. low platelet levels).
Show all 17Show 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 or CBT measurements.
- 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).
- Medications affecting cognition or sleep.
- Presence of any known or suspected obstructive disease of the gastrointestinal tract, including but not limited to diverticulitis and inflammatory bowel disease.
- History of disorders or impairment of the gag reflex.
- Previous gastrointestinal surgery.
- Previous felinization of the esophagus.
- Subjects who might undergo Nuclear Magnetic Resonance (NMR) or MRI scanning during the period that the CorTemp® Disposable Temperature Sensor is within the body.
- Subjects hypomotility disorders of the gastrointestinal tract including but not limited to Ileus.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine
New York, New York, 10016
About this study
Official title: Orexin and Tau Pathology in Cognitively Normal Elderly (A New Prevention Strategy for Alzheimer's Disease)
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Current consensus is that the AD pathological process begins decades before clinical symptoms occur. This long "preclinical" phase of AD might first become detectable in middle-age as deposits of hyperphosphorylated tau (P-tau) in the transentorhinal cortex and subcortical nuclei such as the locus coeruleus (LC) and the nucleus basalis of Meynert. There is strong preliminary evidence showing that cerebrospinal fluid (CSF) levels of orexin-A (OxA) are associated with increased P-tau (r=.52, p<.01) and total-tau (T-tau) (r=.42, p<.01) in cognitively normal older adults (mean age: 69.6±8.6 years).
This study poses that onset of tauopathy in the LC results in down regulation of orexin receptors, leading to a homeostatic increase of OxA production by the hypothalamus, which results in changes in core body temperature (CBT) and sleep disruption that cause further neurodegeneration. This hypothesis will be tested by demonstrating that increases in CSF P-tau are associated in vivo with tau PET uptake, and that tau binding in the LC is associated with increases in CSF OxA (Aim 1); and second, by analyzing the downstream consequences of increased central nervous system (CNS) OxA on sleep architecture and CBT (Aim 2). To test these hypotheses, 19 older adults (age 55-75) balanced by sex, will first perform a full clinical evaluation and PET-MRI where Tau burden will be analyzed by PET-MR using 18F-MK6240 (visits 1-2). Subjects will later undergo 7 days of actigraphy followed by nocturnal polysomnography (NPSG) for 2 consecutive nights (N1-2) during which we will measure CBT (visits 3-4). A morning lumbar puncture (LP) will be performed after N2 to obtain CSF.
Read the detailed description
There is the potential to identify: 1) an association between CSF P-tau and in vivo 18F-MK6240 uptake; 2) a mechanism by which tau pathology may contribute to orexin dysfunction; 3) evidence that orexin dysfunction disrupts sleep and CBT rhythm; and, 4) CNS orexin dysfunction as a new therapeutic target for AD prevention.
- Conditions
- Elderly, Alzheimer Disease
- Being tested
- Actigraphy, Nocturnal Polysomnograpahy (NPSG)
- Keywords
- Orexin, Core Body Temperature
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ActigraphyProcedure or surgery
Recording of sleep/wake cycle and TST by actigraphy to be completed at home by subject over 7 days
Nocturnal Polysomnograpahy (NPSG)Procedure or surgery
N1 habituation and N2 data collection
| Study group | Role | What they receive |
|---|---|---|
| Elderly Patients | Experimental | Not described Receives: Procedure: Actigraphy; Procedure: Nocturnal Polysomnograpahy (NPSG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Spinal Fluid (CSF) P-Tau measured with PET-MR
CSF P-tau is associated with cortical tau uptake
Measured: 4 Weeks
18MK6240 binding amount measured with PET-MR
Tau binding in the brainstem is associated with increases in CSF OxA. PET-MR using 18MK6240 (PET Radiotracer for Imaging Neurofibrillary), which will be performed 1-4 weeks before the LP (visit 2).
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start27 Mar 2018
- Primary completion13 May 2019
- Study completion13 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ElderlyStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 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, M.D, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03053908
- Sponsor's protocol ID
- 16-01529
- Status last verified
- Feb 2021
- First submitted
- 8 Feb 2017
- Last updated
- 24 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Blessing EM, Parekh A, Betensky RA, Babb J, Saba N, Debure L, Varga AW, Ayappa I, Rapoport DM, Butler TA, de Leon MJ, Wisniewski T, Lopresti BJ, Osorio RS. Association between lower body temperature and increased tau pathology in cognitively normal older adults. Neurobiol Dis. 2022 Sep;171:105748. doi: 10.1016/j.nbd.2022.105748. Epub 2022 May 10.
PubMed 35550158
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Orexin and Tau Pathology in Cognitively Normal Elderly (A New Prevention Strategy for Alzheimer's Disease)
- ClinicalTrials.gov ID
- NCT03053908
- Acronym / sponsor ID
- 16-01529
- Conditions
- Elderly, Alzheimer Disease
- Keywords
- Orexin, Core Body Temperature
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 13 May 2019 (actual)
- Study completion
- 13 May 2019 (actual)
- First posted
- 15 Feb 2017 (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 a common neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Current consensus is that the AD pathological process begins decades before clinical symptoms occur. This long "preclinical" phase of AD might first become detectable in middle-age as deposits of hyperphosphorylated tau (P-tau) in the transentorhinal cortex and subcortical nuclei such as the locus coeruleus (LC) and the nucleus basalis of Meynert. There is strong preliminary evidence showing that cerebrospinal fluid (CSF) levels of orexin-A (OxA) are associated with increased P-tau (r=.52, p<.01) and total-tau (T-tau) (r=.42, p<.01) in cognitively normal older adults (mean age: 69.6±8.6 years).
This study poses that onset of tauopathy in the LC results in down regulation of orexin receptors, leading to a homeostatic increase of OxA production by the hypothalamus, which results in changes in core body temperature (CBT) and sleep disruption that cause further neurodegeneration. This hypothesis will be tested by demonstrating that increases in CSF P-tau are associated in vivo with tau PET uptake, and that tau binding in the LC is associated with increases in CSF OxA (Aim 1); and second, by analyzing the downstream consequences of increased central nervous system (CNS) OxA on sleep architecture and CBT (Aim 2). To test these hypotheses, 19 older adults (age 55-75) balanced by sex, will first perform a full clinical evaluation and PET-MRI where Tau burden will be analyzed by PET-MR using 18F-MK6240 (visits 1-2). Subjects will later undergo 7 days of actigraphy followed by nocturnal polysomnography (NPSG) for 2 consecutive nights (N1-2) during which we will measure CBT (visits 3-4). A morning lumbar puncture (LP) will be performed after N2 to obtain CSF.
Detailed description
There is the potential to identify: 1) an association between CSF P-tau and in vivo 18F-MK6240 uptake; 2) a mechanism by which tau pathology may contribute to orexin dysfunction; 3) evidence that orexin dysfunction disrupts sleep and CBT rhythm; and, 4) CNS orexin dysfunction as a new therapeutic target for AD prevention.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Elderly Patients | Experimental | Procedure: Actigraphy, Procedure: Nocturnal Polysomnograpahy (NPSG) |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Not 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 both a Clinical Dementia Rating (CDR)=0 and a MMSE≥27
- All subjects will have had a minimum of 12 years of education. Among minority subjects >80% of the elderly individuals coming to the NYU-ADC meet this criterion. (The education restriction reduces performance variance on cognitive test measures and improves the sensitivity for detecting pathology and disease progression using the robust norms available at NYU. Given the majority of subjects will meet this criterion we do not consider this a major selection bias or generalization limitation for this study).
- An informed family member or life-partner (preferably bed-partner) will be interviewed over the phone or on the first or second visit to confirm the reliability of the subject interview.
Key exclusion criteria (17 listed)
- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders). Subjects with a Fazekas scale >2 will be excluded109.
- Significant history of alcoholism or drug abuse.
- History of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
- Geriatric Depression Scale (short form)>5.
- 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 |
|---|---|---|
| ActigraphyRecording of sleep/wake cycle and TST by actigraphy to be completed at home by subject over 7 days | Procedure or surgery | Elderly Patients |
| Nocturnal Polysomnograpahy (NPSG)N1 habituation and N2 data collection | Procedure or surgery | Elderly Patients |
Primary outcome
Cerebral Spinal Fluid (CSF) P-Tau measured with PET-MR
Time frame: 4 Weeks
CSF P-tau is associated with cortical tau uptake
18MK6240 binding amount measured with PET-MR
Time frame: 2 weeks
Tau binding in the brainstem is associated with increases in CSF OxA. PET-MR using 18MK6240 (PET Radiotracer for Imaging Neurofibrillary), which will be performed 1-4 weeks before the LP (visit 2).
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 24 Feb 2021.
- Derived from this study: PubMed 35550158Blessing EM, Parekh A, Betensky RA, Babb J, Saba N, Debure L, Varga AW, Ayappa I, Rapoport DM, Butler TA, de Leon MJ, Wisniewski T, Lopresti BJ, Osorio RS. Association between lower body temperature and increased tau pathology in cognitively normal older adults. Neurobiol Dis. 2022 Sep;171:105748. doi: 10.1016/j.nbd.2022.105748. Epub 2022 May 10.
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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, M.D principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Actigraphy and Nocturnal Polysomnograpahy (NPSG) in people with Elderly and Alzheimer Disease, run by NYU Langone Health at 1 site 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 17 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 24 Feb 2021. 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 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?
Cerebral Spinal Fluid (CSF) P-Tau measured with PET-MR (time frame: 4 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03053908, which also lists 1 linked publication.
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 24 Feb 2021.