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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG081520-01A1 | U.S. NIH Grant/Contract | View source | |
| 4RF1AG081520-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This study investigates the relationship between the noradrenergic (NA) system, sleep quality, and cognitive function in older adults with insomnia - a population at elevated risk for Alzheimer's disease-related dementias (ADRD) - compared to age and sex matched controls with normal sleep. The study characterizes NA function through multiple approaches: measuring 24-hour plasma levels of norepinephrine (NE) and its brain metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); evaluating central NA system response using the clonidine suppression test (a presynaptic α2 adrenoreceptor agonist that reduces locus coeruleus NA activity; and employing pupillometry as a non-invasive marker of autonomic function. To explore NA function's mechanistic role in insomnia, the study uses an intervention with bright light exposure to enhance daytime NA activity, with the goal of improving both sleep quality and cognitive performance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention on Subjects with Insomnia | Experimental | The intervention in this study will involve 28 (+10) days of daily exposure to bright light (BL) for two 60-minute sessions (morning and afternoon). For the intervention, we will use Re-Timer® light glasses emitting light with an intensity of 230μW/cm2 (~500lux) with a green blue 500nm dominant wavelength (between 480-520nm). Light with these characteristics has been shown effective in suppressing melatonin levels supporting their potential to exert effects on other biological non-visual functions associated with exposure to light relevant for this study. Throughout the intervention, participants will keep a diary to monitor daily use of the glasses. Participants will have weekly phone calls with the research team to encourage compliance and monitor potential side effects. |
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| Dim Red Light | Active Comparator | Participants randomized to the control group will wear for two 60-minute sessions (morning and afternoon) customized dim-red light (RL) control Re-TimerĀ® light glasses (wavelength peak at 632nm, light intensity < 3 lux). Participants will be instructed to wear the light glasses in habitual indoor environments, without engaging in strenuous activities. Throughout the intervention, participants will keep a diary to monitor daily use of the glasses. Participants will have weekly phone calls with the research team to encourage compliance and monitor potential side effects. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Light Exposure | Other | The intervention in this study will involve 28 (+10) days of daily exposure to bright light (BL) for two 60-minute sessions (morning and afternoon). For the intervention, we will use Re-Timer® light glasses emitting light with an intensity of 230μW/cm2 (~500lux) with a green blue 500nm dominant wavelength (between 480-520nm). Light with these characteristics has been shown effective in suppressing melatonin levels supporting their potential to exert effects on other biological non-visual functions associated with exposure to light relevant for this study. Throughout the intervention, participants will keep a diary to monitor daily use of the glasses. Participants will have weekly phone calls with the research team to encourage compliance and monitor potential side effects. |
| Measure | Description | Time Frame |
|---|---|---|
| 24h plasma norepinephrine | 24-h plasma norepinephrine (pg/mL) collected every two hours | Enrollment to the end of treatment at 10 weeks. |
| Clonidine suppression test | Plasma norepinephrine levels (pg/mL) and 3- plasma 3-methoxy-4-hydroxyphenylglycol (MHPG, ng/mL) levels in response to clonidine suppression test. Collected at baseline and every 30 minutes for 2 hours after clonidine ingestion. | Enrollment |
| Wake after sleep onset (WASO) | Duration in minutes obtained from polysomnography and actigraphy | Enrollment to the end of treatment at 10 weeks. |
| Slow oscillatory activity during sleep | SO activity (0.5 - 1Hz) is measured from EEG during in laboratory stay | Enrollment to the end of treatment at 10 weeks. |
| Pittsburg Sleep Quality Index | Self administered questionnaire to evaluate subjective sleep quality | Enrollment to the end of treatment at 10 weeks. |
| NIH tool box | Cognitive battery to assess executive functions, attention, episodic and working memory | Enrollment to the end of treatment at 10 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| 24-h plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) | MHPG (ng/mL) is the main metabolite of Norepinephrine from the brain measured in plasma. | Enrollment to the end of treatment at 10 weeks. |
| 24-h plasma cortisol levels |
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Inclusion Criteria:
Inclusion criteria for the insomnia group:
Inclusion criteria for the control group:
Exclusion Criteria:
17.Use of weight-loss medications
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marguerite McGuire | Contact | 844-707-5337 | marguerite.mcguire@northwestern.edu | |
| Daniela Grimaldi, MD, PhD | Contact | 844-707-5337 | daniela.grimaldi@northwestern.edu |
| Name | Affiliation | Role |
|---|---|---|
| Daniela Grimaldi, MD, PhD | Northwestern University | Principal Investigator |
| Phyllis C Zee, MD, PhD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Feinberg School of Medicine, Center for Circadian and Sleep Medicine | Recruiting | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35124476 | Background | Van Egroo M, Koshmanova E, Vandewalle G, Jacobs HIL. Importance of the locus coeruleus-norepinephrine system in sleep-wake regulation: Implications for aging and Alzheimer's disease. Sleep Med Rev. 2022 Apr;62:101592. doi: 10.1016/j.smrv.2022.101592. Epub 2022 Jan 21. | |
| 6228698 | Background | Mann DM. The locus coeruleus and its possible role in ageing and degenerative disease of the human central nervous system. Mech Ageing Dev. 1983 Sep;23(1):73-94. doi: 10.1016/0047-6374(83)90100-8. |
| Label | URL |
|---|---|
| Center for Circadian and Sleep Medicine Website | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| Study Overview and Intial Screening Eligibility Form | View IPD |
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| Placebo | Other | Participants randomized to the control group will wear for two 60-minute sessions (morning and afternoon) customized dim-red light (RL) control Re-TimerĀ® light glasses (wavelength peak at 632nm, light intensity < 3 lux). |
|
24-h plasma cortisol levels (nmol/L) collected every two hours as a measure of autonomic activation
| Enrollment to the end of treatment at 10 weeks. |
| 24h plasma melatonin | 24-h plasma melatonin (pg/mL) collected every two hour as a circadian measure | Enrollment to the end of treatment at 10 weeks. |
| Pupillometry | Pupil size (measure of autonomic activation) | Enrollment to the end of treatment at 10 weeks. |
| Psychomotor Vigilance Test | To assess reaction time (ms) | Enrollment to the end of treatment at 10 weeks. |
| Wake EEG | EEG power in alpha band during wake to measure vigilance levels | Enrollment to the end of treatment at 10 weeks. |
| Heart Rate and Heart Rate Variability | HR (bpm) and measures of HRV variability (high frequency (HF) component and low frequency to high frequency ratio LF/HF to assess autonomic function and sympatho-vagal balnce | Enrollment to the end of treatment at 10 weeks. |
| Insomnia Severity Index | Questionnaire to measure insomnia severity | Enrollment to the end of treatment at 10 weeks. |
| Visual Analogue Scale | Scale to measure global vigor ( score 0 to 100) and global alertness (0 to 100). Higher scores indicate greater levels of both vigor and positive affect. | Enrollment to the end of treatment at 10 weeks. |
| 15872097 | Background | Cirelli C, Huber R, Gopalakrishnan A, Southard TL, Tononi G. Locus ceruleus control of slow-wave homeostasis. J Neurosci. 2005 May 4;25(18):4503-11. doi: 10.1523/JNEUROSCI.4845-04.2005. |
| 15980285 | Background | McCrae CS, Rowe MA, Tierney CG, Dautovich ND, Definis AL, McNamara JP. Sleep complaints, subjective and objective sleep patterns, health, psychological adjustment, and daytime functioning in community-dwelling older adults. J Gerontol B Psychol Sci Soc Sci. 2005 Jul;60(4):P182-9. doi: 10.1093/geronb/60.4.p182. |
| 23814339 | Background | Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA. Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons. Sleep. 2013 Jul 1;36(7):1027-1032. doi: 10.5665/sleep.2802. |
| 28890168 | Background | Shi L, Chen SJ, Ma MY, Bao YP, Han Y, Wang YM, Shi J, Vitiello MV, Lu L. Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Med Rev. 2018 Aug;40:4-16. doi: 10.1016/j.smrv.2017.06.010. Epub 2017 Jul 6. |
| REDCap Initial Screening Eligibility Form | View source |
Full protocol available via email request: CCSMresearch@northwestern.edu |
| D001523 |
| Mental Disorders |