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

Inflammation Clinical Trial

Official title:

Associations of Adverse Childhood Experiences, Sleep Disruption, and Vascular Dysfunction in Young Adults: The Iowa ACEs and Sleep Cohort and Manipulating Sleep in Young Adults With ACEs Studies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06454344
• Other study ID #: 202307139
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: October 31, 2028

Study information

• Verified date: June 2024
• Source: University of Iowa
• Contact: Nathaniel D Jenkins, PhD
• Phone: 3194673091
• Email: nathaniel-jenkins[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: October 31, 2028
• Est. primary completion date: October 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 29 Years

Eligibility

AIM 1

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. PSQI 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.

Related Conditions & MeSH terms

• Adverse Childhood Experiences
• Aneurysm
• Endothelial Dysfunction
• Inflammation
• Oxidative Stress
• Psychological Trauma
• Psychosocial Stressor
• Sleep
• Sleep Disturbance

Intervention

Behavioral:
• Cognitive Behavioral Therapy for Insomnia (CBT-i)
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.

Locations

Country	Name	City	State
United States	Integrative Laboratory of Applied Physiology and Lifestyle Medicine	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Nathaniel Jenkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Other	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)
Other	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)
Other	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)
Primary	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)
Secondary	Endothelial NF?B p65 expression.	Vascular endothelial cells will be biopsied and stained for inflammatory marker NF?B p65.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Secondary	Endothelial TNF-a expression.	Vascular endothelial cells will be biopsied and stained for inflammatory marker TNF-a.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Circulating CRP	Blood samples will be collected and analyzed for inflammatory marker CRP in plasma.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Secondary	Circulating TNF-a	Blood samples will be collected and analyzed for inflammatory marker TNF-a in serum.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Circulating 8-iso prostaglandin F2a	Blood samples will be collected and analyzed for oxidative stress marker 8-iso prostaglandin F2a in serum.	Week 0 (Pre-Intervention) and Week 7 (Post-Intervention)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)