Clinical trial NCT06535178: The Influence of Sleep on Cardiovascular Outcomes
Official title: Determining the Influence of Sleep on Cardiovascular Outcomes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Circadian Rhythm
Cardiometabolic Health
Vascular Health
Keywords: Circadian Rhythm
Cardiometabolic Health
Vascular Health
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Medical Research Foundation, Oregon
First posted: 2024-08-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The goal of this study is to identify the effects of sleep regularity on cardiovascular regulatory mechanisms. The investigators are hoping to discover if improving the regularity of sleep timing will improve metabolic and vascular health markers. The protocol is a 12-week prospective cohort study that includes both field and in-laboratory data collection in ostensibly healthy male and female adults, aged 18-40years.

Detailed description: Sleep is a fundamental determinant of heath; however, the impact of day-to-day variations in sleep patterns (i.e., sleep regularity) on cardiometabolic and vascular health has been underappreciated. Emerging evidence suggests that less regularity in sleep timing is correlated with cardiometabolic health and is a stronger predictor of mortality risk than sleep duration. In this cohort, the investigators will determine the influence of sleep regularity on mechanisms that impact cardiometabolic, vascular, and autonomic function.

The misalignment of behaviors (e.g., sleep) with the internal timing system (i.e., circadian misalignment) is likely a mechanistic contributor to unfavorable health outcomes. Laboratory experiments have shown that acute circadian misalignment increases markers of inflammation, alters metabolism, and elevates mean arterial pressure. We have shown that poorer overnight blood pressure dipping patterns are associated with circadian disruptions elicited by decreased sleep regularity, which occurs within 90-days of transitioning to a shift work schedule. There is a need to characterize the influence of sleep regularity on the underlying pathways that affect health.

The goal of this study is to determine the effect of an intervention targeting improved sleep regularity on circadian, metabolic, and vascular health markers. Participants within the lowest tertile for sleep regularity will adhere to a consistent sleep onset time (±30 min) for approximately 12-weeks. The outcomes that the investigators will focus on will be indices of hemodynamics (blood pressure, heart rate, autonomic function), blood biomarkers (markers of inflammation, oxidative stress, and triglycerides), energy metabolism, weight, and percent body fat.

1. Outpatient Biobehavioral Weeks: Actigraphy data will be collected across 2-weeks to assess habitual sleep patterns and calculate a sleep regularity index (SRI).
2. Biobehavioral Laboratory Visit: Participants will be asked to visit the OHSU School of Nursing (SON) Biobehavioral Laboratory space for two in-laboratory visits in dim-light settings, which will involve an evening stay (\~7.5h) to measure circadian markers, body composition, vascular function, and questionnaire data. Saliva samples will also be collected via salivettes in order to measure the hormone melatonin and determine each participants' dim-light melatonin onset (DLMO). Participants lowest SRI tertile (intervention group) will be instructed to maintain a consistent sleep onset time (±30 min self-selected sleep time) for up to 12-weeks. Compliance will be assessed across 6-weeks of outpatient bio-behavioral data collection via sleep logs, actigraphy, and daily surveys (described below). All other participants (control group) will be instructed to maintain their habitual sleep patterns for up to 12-weeks.
3. Ambulatory Monitoring: For participants in the intervention group, biobehavioral data collection will occur at Weeks 1-2, Weeks 6-7, and Weeks 11-12. For the control group, biobehavioral data collection will occur at Weeks 11-12. During these weeks, participants will wear an actigraphy device and keep sleep logs for 2-weeks during the biobehavioral data collection. Participants will also wear an ambulatory blood pressure cuff. Additionally, to measure glucose levels throughout the protocol, participants will be fitted with a continuous glucose monitor. Participants will complete daily surveys each bio-behavioral period to measure self-reported bed and wake times and naps.
4. Blood Biomarkers: At baseline and at Week 12, participants will visit the SON Biobehavioral Laboratory for a blood draw to obtain markers of inflammation, oxidative stress, and lipemic markers that will be measured with an \~10mL blood draw.

Eligibility criteria: Inclusion Criteria:

- Ostensibly healthy men and women

Exclusion Criteria:

* No history of drug or alcohol dependency.
* Must be current non-smokers, and are required to have a history of less than 5 pack years of smoking.
* No history of working irregular day and night hours, regular night work, or rotating shift work for the 1 year prior to the study. In addition to this, individuals must not have traveled across more than 1 time zone during the 3 months prior to the study.
* Chronobiologic and sleep disorders.
* Diseases of the cardiovascular system.
* Hypertension. Individuals will be allowed to be normotensive (resting systolic blood pressure of \<140/90 mmHg, measured on more than one occasion) or uncomplicated stage 1 hypertension (systolic BP between 140 and 159 mmHg or a diastolic BP between 90 and 99 mmHg).
* Disorders of the respiratory system.
* Pre-diabetes/Diabetes. For participants who have self-reported pre-diabetes/diabetes.
* Disorders of the kidney and urinary tract.
* Infectious diseases.
* Disorders of the gastrointestinal system.
* Disorders of the immune system.
* Disorders of the hematopoietic system.
* Neoplastic diseases.
* Endocrine and metabolic diseases.
* Neurologic disorders.
* Must not be participating in another research study that would influence their safe participation in the study.

Primary outcomes:
measure: Changes in dim-light melatonin onset
timeFrame: Week 0 and Week 12
measure: Changes in SRI
timeFrame: Week 0 and Week 12
measure: Changes in vascular endothelial function
timeFrame: Week 0 and Week 12
measure: Changes in heart rate
timeFrame: Week 0 and Week 12
measure: Changes in blood pressure
timeFrame: Week 0 and Week 12
measure: Changes in resting cardiac vagal tone
timeFrame: Week 0 and Week 12
measure: Changes in heart rate response to exercise
timeFrame: Week 0 and Week 12
measure: Changes in blood pressure response to exercise
timeFrame: Week 0 and Week 12
measure: Changes in energy metabolism
timeFrame: Week 0 and Week 12
measure: Changes in glucose
timeFrame: Week 0 and Week 12
Secondary outcomes:
measure: Changes in MDA
timeFrame: Week 0 and Week 12
measure: Changes in TAC
timeFrame: Week 0 and Week 12
measure: Changes in CRP
timeFrame: Week 0 and Week 12
measure: Changes in triglycerides
timeFrame: Week 0 and Week 12
measure: Changes in percent body fat
timeFrame: Week 0 and Week 12
measure: Changes in weight
timeFrame: Week 0 and Week 12
measure: Changes in BMI
timeFrame: Week 0 and Week 12
measure: Changes in PIPR
timeFrame: Week 0 and Week 12
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Andrew W McHill, PhD
role: PRINCIPAL_INVESTIGATOR
References: