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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL167788-01A1 | U.S. NIH Grant/Contract | View source |
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The overall purpose of this study is to understand the role of disrupted sleep in the association of exposure to early life adversity (adverse childhood experiences (ACEs)) with vascular endothelial (dys)function.
In Aim 1 (The Iowa ACEs and Sleep Cohort Study), the investigators will utilize a cross-sectional cohort design with a state-of-the-art translational approach. Participants will be recruited to objectively characterize the degree to which lower sleep quality and quantity contribute to ACEs-related endothelial dysfunction, inflammation, and oxidative stress in young adults using:
In Aim 2, approximately 70 eligible participants from Aim 1 (The Iowa ACEs and Sleep Cohort Study) will then be randomized to either a 6-week behavioral sleep intervention (cognitive behavioral therapy for insomnia) or a wait-list control to determine the mechanistic contribution of sleep disruption to vascular dysfunction in young adults with moderate-to-high exposure to adverse childhood experiences (ACEs). Following the intervention, participants will again complete:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cognitive Behavioral Therapy for Insomnia (CBT-i) | Experimental |
| |
| Waitlist Control | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive Behavioral Therapy for Insomnia (CBT-i) | Behavioral | CBT-I is a structured program with a robust empirical evidence supporting its efficacy for improving sleep quality and quantity. The cognitive component of CBT-I teaching individuals how to recognize and change the beliefs they hold about sleep that negatively impact sleep, such as negative thoughts and emotions. The behavioral component includes several strategies to help improve sleep, including: improved sleep hygiene, improving the sleep environment, relaxation training, stimulus control therapy (consistent wake/sleep times, using the bed only for sleep, etc), and sleep restriction. Sleep restriction consists of reducing the time spend in bed initially to increase sleep drive in subsequent nights. Once sleep has improved, the time in bed is gradually increased again. |
| Measure | Description | Time Frame |
|---|---|---|
| Vascular Endothelial Function | The brachial artery flow-mediated dilation (FMD) technique, a non-invasive bioassay of endothelium-dependent vasodilatory function, will be used as the primary determinant of in-vivo vascular endothelial function. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial NFκB p65 expression. | Vascular endothelial cells will be biopsied and stained for inflammatory marker NFκB p65. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Endothelial TNF-α expression. |
| Measure | Description | Time Frame |
|---|---|---|
| Sleep Quality | The investigators will objectively quantify sleep quality as actigraphy measured as sleep efficiency (PRIMARY independent variable) and wakefulness after sleep onset and PSG measured sleep depth as indicated by the relative time spent in slow wave sleep. The investigators will also assess sleep efficiency and wakefulness after sleep onset using sleep diaries. These parameters are considered the independent variable in this study, with the primary identified independent variable identified as sleep efficiency. Collection of these data will be used to a) confirm changes and b) examine whether changes in the variables do in fact mediate changes in vascular function. |
AIM 1
Inclusion Criteria:
Exclusion Criteria:
AIM 2
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nathaniel D Jenkins, PhD | Contact | 3194673091 | nathaniel-jenkins@uiowa.edu |
| Name | Affiliation | Role |
|---|---|---|
| Nathaniel Jenkins, PhD | Assistant Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Integrative Laboratory of Applied Physiology and Lifestyle Medicine | Recruiting | Iowa City | Iowa | 52242 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 27, 2023 | Jun 1, 2024 |
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Vascular endothelial cells will be biopsied and stained for inflammatory marker TNF-α.
| Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Endothelial MCP-1 expression. | Vascular endothelial cells will be biopsied and stained for inflammatory marker MCP-1. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Endothelial NADPH-oxidase p47phox expression. | Vascular endothelial cells will be biopsied and stained for NADPH-oxidase p47phox, a marker of oxidative stress. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Endothelial nitrotyrosine expression. | Vascular endothelial cells will be biopsied and stained for nitrotyrosine, a marker of oxidative stress. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating CRP | Blood samples will be collected and analyzed for inflammatory marker CRP in plasma. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating TNF-α | Blood samples will be collected and analyzed for inflammatory marker TNF-α in serum. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating MCP-1 | Blood samples will be collected and analyzed for inflammatory marker MCP-1 in serum. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating IL1-RA | Blood samples will be collected and analyzed for inflammatory marker IL1-RA in plasma. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating oxidized low density lipoprotein | Blood samples will be collected and analyzed for oxidative stress marker oxidized low density lipoprotein in serum. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Circulating 8-iso prostaglandin F2α | Blood samples will be collected and analyzed for oxidative stress marker 8-iso prostaglandin F2α in serum. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Anti-oxidant (Superoxide Dismutase) Activity in Peripheral Blood Mononuclear Cells | Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and superoxide dismutase activity will be quantified using calorimetric assay. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Anti-oxidant (Glutathione Reductase) Activity in Peripheral Blood Mononuclear Cells | Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and glutathione reductase activity will be quantified using calorimetric assay. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Anti-oxidant (Catalase) Activity in Peripheral Blood Mononuclear Cells | Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and catalase activity will be quantified using calorimetric assay. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Perceived Stress | The investigators will measure perceived stress using the "Perceived Stress Scale" (PSS-10). This will be considered one of the mediators alongside sleep in the investigators' models, as the addition of other potential mediators can improve power and provide a more accurate estimate of the original (sleep) mediator by controlling for shared effects among mediators. The PSS-10 has a minimum score of "0" and a maximum score of "40" with higher scores indicating worse outcomes. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Distress | The investigators will measure distress using the "Kessler Psychological Distress Scale" (K-10). This will be considered one of the mediators alongside sleep in the investigators' models, as the addition of other potential mediators can improve power and provide a more accurate estimate of the original (sleep) mediator by controlling for shared effects among mediators. The K-10 has a minimum score of "10" and a maximum score of "50" with higher scores indicating worse outcomes. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Sleep Duration | The investigators will objectively quantify total sleep duration using actigraphy and via sleep diary. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Anxiety and Depression | Anxiety and depression symptoms will be assessed using the "Inventory of Depression and Anxiety Symptoms-II" (IDAS-II), which is a reliable, well-validated assessment of mood and anxiety disorder symptoms. Using this scale, anxiety and depression ill be well-measured, and the investigators will assess their role as confounders/mediators in analyses. Each scale is individually assessed, meaning that the minimum score for mood symptoms, specifically, ranges from 3-20, and the maximum score ranges from 15-100 for this scale. With regards to anxiety disorder symptoms, the minimum score ranges from 3-8, and the maximum score ranges from 15-40. Higher scores on scales indicate worse outcomes. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| Trauma | Trauma symptoms will be assessed using the "PTSD Checklist for DSM-5" (PCL-5) with Life Events checklist. Using this scale, trauma symptoms will be well-measured, and the investigators will assess their role as confounders/mediators in analyses. The minimum value for this scale is "0" and the maximum value for this scale is "80". Higher scores on this scale indicate a worse outcome. | Week 0 (Pre-Intervention) and Week 7 (Post-Intervention) |
| SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 1, 2024 | Jun 1, 2024 | ICF_001.pdf |
| ID | Term |
|---|---|
| D000783 | Aneurysm |
| D020447 | Parasomnias |
| D000067073 | Psychological Trauma |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
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