Sleep, Blood Pressure and Vascular Health

The investigators hypothesize that chronic insufficient sleep is associated with diminished endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Furthermore, the investigators hypothesize that the postulated diminishment in endothelial vasodilator and fibrinolytic function with insufficient sleep will be due, at least in part, to increased oxidative stress. Furthermore, increasing sleep duration and improving sleep quality will increase both endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Increases in endothelial vasodilator and fibrinolytic function will be due, at least in part, to reduced oxidative stress.

Study Overview

• Status: Completed
• Conditions: Sleep; Blood Pressure
• Intervention / Treatment: Other: Targeted Sleep Intervention

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • UC-Boulder Clinical and Translational Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects will be men and women of all races and ethnic backgrounds aged 45-65 years.

All women will be premenopausal, perimenopausal or post-menopausal not taking hormone replacement therapy.

Subjects will be prehypertensive/hypertensive (Stage 1 hypertension) defined as resting systolic blood pressure 125-159 mmHg and/or diastolic blood pressure 75-99 mmHg.

Subjects will have no overt signs of disease as assessed by:

1. medical history;
2. physical examination;
3. electrocardiogram and BP at rest and maximal exercise;
4. sedentary as determined from the Stanford Physical Activity Questionnaire (<35 kcal/wk) and will not have engaged in any program of regular physical activity for at least 6 months prior to the study.
5. Subjects that have a pre-existing diagnosis of obstructive sleep apnea, or are determined to have obstructive sleep apnea based on their sleep disorders screening visit will be allowed in the study, but will not take part in the sleep intervention/post sleep intervention visits.

Exclusion Criteria:

History of stroke (phone screen and medical record) Peripheral vascular disease (phone screen and medical record) History of anaphylaxis to betadine, lidocaine, iodine Body mass index > 40 kg/m2

Subjects taking blood pressure-or diabetes related medication Chronic Insomnia (prior or current diagnosis) History of or current psychiatric disorder (e.g., prior or current diagnosis, current BDI-II>13; BAI>10) Significant organ system dysfunction/disease (e.g. diabetes, severe pulmonary, kidney disease) History of seizure disorder Pregnant/nursing Positive toxicology screen-(THC, OPI, AMP, COC, PCP, BAR, BZO, MAMP/MDMA upon sleep lab admission)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Phase 1; Phase I is a cross-sectional study to compare endothelial vasodilator and fibrinolytic function in adults with elevated blood pressure who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 6.5 hr/night (short sleep)
Experimental: Phase 2; Phase II is an intervention study to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator and fibrinolytic function in adults with elevated blood pressure who habitually sleep less than 6.5 hr/night (Specific Aims 3).	Other: Targeted Sleep Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Systolic Blood Pressure (SBP)		SBP will be measured during Phase 1 at the participants week 1 visit.
Phase 2: Systolic Blood Pressure (SBP)	SBP measured following the participants 8 week sleep intervention	SBP will be measured during Phase 2 at the participants week 8 visit.
Phase 1: Diastolic Blood Pressure (DBP)		DBP will be measured during Phase 1 at the participants week 1 visit.
Phase 2: Diastolic Blood Pressure (DBP)	DBP measured following the participants 8 week sleep intervention	DBP wwill be measured during Phase 2 at the participants week 8 visit.
Phase 1: Forearm blood flow (FBF) response to Acetylcholine (ACh)		FBF response to ACh will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Phase 2: FBF response to Acetylcholine (ACh)	FBF to ACh will be measured following the participants 8 week sleep intervention	FBF response to ACh will be measured during Phase 2 at the participants visit 9 which is ~13 weeks from their respective start date.
Phase 1: FBF response to Sodium Nitroprusside (NTP)		FBF response to NTP will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Phase 2: FBF response to Sodium Nitroprusside (NTP)	FBF to NTP will be measured following the participants 8 week sleep intervention	FBF response to NTP will be measured during Phase 2 at the participants visit 9 which is ~13 weeks from their respective start date.
Phase 1: Endothelial t-PA Release in response to Bradykinin (BDK)		t-PA release will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Phase 2: Endothelial t-PA Release in response to Bradykinin (BDK)	Endothelial t-PA release will be measured following the participants 8 week sleep intervention.	t-PA release will be measured during Phase 2 at the participants visit 9 which is ~13 weeks from their respective start date.
Phase 1: FBF response to L-NMMA		FBF response to L-NMMA will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Phase 2: FBF response to L-NMMA	FBF to L-NMMA will be measured following the participants 8 week sleep intervention.	FBF response to L-NMMA will be measured during Phase 2 at the participants visit 9 which is ~13 weeks from their respective start date.
Phase 1: FBF response to ACh+L-NMMA		FBF response to ACh+L-NMMA will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Phase 2: FBF response to ACh+L-NMMA	FBF to ACh+L-NMMA will be measured following the participants 8 week sleep intervention	FBF response to ACh+L-NMMA will be measured during Phase 2 at the participants visit 9 which is ~13 weeks from their respective start date.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Pittsburgh Sleep Quality Index (PSQI)	This questionnaire assesses sleep quality. Scores range from 0 indicating no difficulty and 21 indicating severe difficulty.	The PSQI questionnaire will be administered during Phase 1 at the participants week 1 visit.
Phase 2: PSQI	This questionnaire assesses sleep quality. Scores range from 0 indicating no difficulty and 21 indicating severe difficulty.	The PSQI questionnaire will be administered during Phase 2 at the participants week 8 visit.
Phase 1: Insomnia Severity Index	This questionnaire is used to assess the nature and severity of insomnia. Scores range from 0 no insomnia to 28 severe insomnia.	The insomnia severity index questionnaire will be administered during Phase 1 at the participants week 1 visit.
Phase 2: Insomnia Severity Index	This questionnaire is used to assess the nature and severity of insomnia. Scores range from 0 no insomnia to 28 severe insomnia.	The insomnia severity index questionnaire will be administered during Phase 2 at the participants week 8 visit.
Phase 1: Epworth Sleepiness Scale	This questionnaire is used to assess daytime sleepiness. Scores range from 0 normal daytime sleepiness to 24 severe daytime sleepiness.	The Epworth Sleepiness scale questionnaire will be administered during Phase 1 at the participants week 1 visit.
Phase 2: Epworth Sleepiness Scale	This questionnaire is used to assess daytime sleepiness. Scores range from 0 normal daytime sleepiness to 24 severe daytime sleepiness.	The Epworth Sleepiness scale questionnaire will be administered during Phase 2 at the participants week 8 visit.

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Investigators: Principal Investigator: Christopher DeSouza, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2016
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 160646

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No