The Iowa ACEs and Sleep Cohort and Manipulating Sleep in Young Adults With ACEs Studies

Not Applicable

Recruiting

• Conditions: Sleep Disturbance; Vascular Dilatation; Psychological Trauma; Psychosocial Stressor; Inflammation; Sleep; Endothelial Dysfunction; Adverse Childhood Experiences; Oxidative Stress
• Interventions: Behavioral: Cognitive Behavioral Therapy for Insomnia (CBT-i)

• Registration Number: NCT06454344
• Lead Sponsor: Nathaniel Jenkins

Brief Summary

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:

1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration,

2. in vivo assessment of endothelial function via flow-mediated dilation testing, and

3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells. This study to achieve this Aim.

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:

1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration,

2. in vivo assessment of endothelial function via flow-mediated dilation testing, and

3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-03
• Study First Submitted: 2024-06-03
• Study First Submitted QC: 2024-06-09
• Study First Posted: 2024-06-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-20
• Primary Completion: 2027-10-31
• Study Completion: 2028-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. 18-29 years of age
2. SBP <129 and DBP <90 mmHg
3. Body Mass Index > 18.5 kg/m2 and <35 kg/m2
4. Willing to complete in-home sleep studies

Exclusion Criteria

1. Currently undergoing treatment for a sleep disorder or diagnosed with restless leg syndrome, hypersomnia, parasomnia or narcolepsy, or obstructive sleep apnea
2. Currently performing overnight shift work
3. Lifetime history of any psychiatric disorder with psychotic features or bipolar disorder, currently undergoing treatment for substance-induced mood disorder
4. Endorsed suicidal ideation as indicated by a Moderate or High risk determination on the Columbia Suicide Risk Protocol
5. Diagnosed neurological disorder or illness affecting the central nervous system
6. Diagnosed acute or chronic autoimmune disease or chronic inflammatory condition
7. Current or previous cancer diagnosis
8. History of moderate or severe traumatic brain injury
9. Current or previous history of CBT-I treatment or sleep restriction or cognitive restructuring therapy for sleep
10. History of cardiometabolic disease (e.g., ischemic heart disease, coronary artery disease, stroke, chronic kidney disease, diabetes mellitus), pulmonary disease, or renal disease
11. Current or recent (within past month) use of anti-hypertensive (including clonidine), lipid lowering, glucose- controlling, or prescription anti-inflammatory medications
12. Current or recent (within past month) opiates, benzodiazepine or benzodiazepine receptor agonists, or trazodone
13. Recent changes to or unstable treatment (changes within last 6 mo.) with prescription medications
14. Currently smoking or using nicotine
15. Current use of hormone therapy
16. Current heavy alcohol use, as defined as binge drinking on 5 or more days in the last month, or consuming more than 7 (women) or 14 (men) drinks per week in the last month (per NIAAA definition)
17. Current or recent (within the last 6 mo.) illicit drug use disorder as indicated by a score of 3 or greater on the Drug Abuse Screening Test (DAST-10)
18. Current or recent (within 6 mo.) pregnancy OR current or recent breastfeeding (within 3 mo.) OR children under the age of 2 years old in the home
19. Currently completing greater than 300 minutes of moderate intensity, or greater than 150 minutes of vigorous intensity physical activity, or an equal combination per week
20. Unstable housing

AIM 2

Inclusion Criteria:

1. 18-29 years of age
2. SBP <129 and DBP <90 mmHg
3. Body Mass Index > 18.5 kg/m2 and <35 kg/m2
4. Willing to complete in-home sleep studies
5. >= 3 Adverse Childhood Experiences
6. PSQI Global Score >5
7. Sleep Efficiency Score <90%

Exclusion Criteria:

1. Currently undergoing treatment for a sleep disorder or diagnosed with restless leg syndrome, hypersomnia, parasomnia or narcolepsy, or obstructive sleep apnea
2. Currently performing overnight shift work
3. Lifetime history of any psychiatric disorder with psychotic features or bipolar disorder, currently undergoing treatment for substance-induced mood disorder
4. Endorsed suicidal ideation as indicated by a Moderate or High risk determination on the Columbia Suicide Risk Protocol
5. Diagnosed neurological disorder or illness affecting the central nervous system
6. Diagnosed acute or chronic autoimmune disease or chronic inflammatory condition
7. Current or previous cancer diagnosis
8. History of moderate or severe traumatic brain injury
9. Current or previous history of CBT-I treatment or sleep restriction or cognitive restructuring therapy for sleep
10. History of cardiometabolic disease (e.g., ischemic heart disease, coronary artery disease, stroke, chronic kidney disease, diabetes mellitus), pulmonary disease, or renal disease
11. Current or recent (within past month) use of anti-hypertensive (including clonidine), lipid lowering, glucose- controlling, or prescription anti-inflammatory medications
12. Current or recent (within past month) opiates, benzodiazepine or benzodiazepine receptor agonists, or trazodone
13. Recent changes to or unstable treatment (changes within last 6 mo.) with prescription medications
14. Currently smoking or using nicotine
15. Current use of hormone therapy
16. Current heavy alcohol use, as defined as binge drinking on 5 or more days in the last month, or consuming more than 7 (women) or 14 (men) drinks per week in the last month (per NIAAA definition)
17. Current or recent (within the last 6 mo.) illicit drug use disorder as indicated by a score of 3 or greater on the Drug Abuse Screening Test (DAST-10)
18. Current or recent (within 6 mo.) pregnancy OR current or recent breastfeeding (within 3 mo.) OR children under the age of 2 years old in the home
19. Currently completing greater than 300 minutes of moderate intensity, or greater than 150 minutes of vigorous intensity physical activity, or an equal combination per week
20. Unstable housing
21. Likely Obstructive Sleep Apnea, as indicated by an apnea-hypopnea index (AHI) >= 15 events/hour or persistent hypoxemia, as indicated by an arterial oxygen saturation <= 88% for >5 minutes per night.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive Behavioral Therapy for Insomnia (CBT-i)	Cognitive Behavioral Therapy for Insomnia (CBT-i)	-

Primary Outcome Measures

Name	Time	Method
Vascular Endothelial Function	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	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.

Secondary Outcome Measures

Name	Time	Method
Endothelial nitrotyrosine expression.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Vascular endothelial cells will be biopsied and stained for nitrotyrosine, a marker of oxidative stress.
Circulating IL1-RA	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for inflammatory marker IL1-RA in plasma.
Anti-oxidant (Superoxide Dismutase) Activity in Peripheral Blood Mononuclear Cells	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and superoxide dismutase activity will be quantified using calorimetric assay.
Anti-oxidant (Glutathione Reductase) Activity in Peripheral Blood Mononuclear Cells	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and glutathione reductase activity will be quantified using calorimetric assay.
Endothelial NFκB p65 expression.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Vascular endothelial cells will be biopsied and stained for inflammatory marker NFκB p65.
Endothelial TNF-α expression.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Vascular endothelial cells will be biopsied and stained for inflammatory marker TNF-α.
Endothelial MCP-1 expression.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Vascular endothelial cells will be biopsied and stained for inflammatory marker MCP-1.
Circulating CRP	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for inflammatory marker CRP in plasma.
Circulating oxidized low density lipoprotein	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for oxidative stress marker oxidized low density lipoprotein in serum.
Circulating 8-iso prostaglandin F2α	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for oxidative stress marker 8-iso prostaglandin F2α in serum.
Endothelial NADPH-oxidase p47phox expression.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Vascular endothelial cells will be biopsied and stained for NADPH-oxidase p47phox, a marker of oxidative stress.
Anti-oxidant (Catalase) Activity in Peripheral Blood Mononuclear Cells	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Peripheral blood mononuclear cells will be isolated from whole blood pre and post intervention and catalase activity will be quantified using calorimetric assay.
Perceived Stress	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	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.
Distress	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	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.
Circulating TNF-α	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for inflammatory marker TNF-α in serum.
Circulating MCP-1	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)	Blood samples will be collected and analyzed for inflammatory marker MCP-1 in serum.

Trial Locations

Locations (1)

Integrative Laboratory of Applied Physiology and Lifestyle Medicine; 🇺🇸 Iowa City, Iowa, United States