HIV-1, Insufficient Sleep and Vascular Endothelial Dysfunction

Study Overview
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Brief Summary
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The investigators hypothesize that chronic insufficient sleep is associated with diminished endothelium-dependent nitric oxide-mediated vasodilation and tissue-type plasminogen activator release in anti-retroviral (ART)-treated HIV-1-seropositive adults. 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. Moreover, increasing sleep duration and improving sleep quality will increase both endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in ART-treated HIV-1-seropositive adults. Increases in endothelial vasodilator and fibrinolytic function will be due, at least in part, to reduced oxidative stress.

Official Title
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HIV-1, Insufficient Sleep and Vascular Endothelial Dysfunction

Conditions
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HIV-1

Intervention / Treatment
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* Behavioral: Individualized Targeted Sleep


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be men and women of all races and ethnic backgrounds aged 40-75 years with documented HIV-1 infection. Subjects will be HIV-1-seropositive individuals on a stable DHHS approved ART regimen for at least 6 months, with documented virologic suppression (<50 copies HIV-1 RNA/mL) for at least 3 months. All subjects must have CD4+ T cell counts >200 cells/mm3 at the time of study entry. Subjects will be free of overt CVD as assessed by: a) medical history; b) physical examination; c) electrocardiogram and BP at rest and maximal exercise; d) complete blood chemistries, lipid and lipoprotein, glucose, insulin and hematological evaluation. All candidates will be 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. Exclusion Criteria: Receiving hormone replacement therapy (HRT) currently or in the preceeding 3-year period. Pre- or peri-menopausal women

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Phase 1<br>Phase 1 is a cross-sectional study to compare endothelial vasodilator and fibrinolytic function in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). | |
| Experimental: Phase 2<br>Phase 2 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 ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night. | Behavioral: Individualized Targeted Sleep<br>* The investigators will employ an 8-week individualized targeted sleep intervention. Individualized targeted interventions have the advantage of improving adherence, reducing attrition, and making the strategy personally meaningful.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 me 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  11 weeks from their respective start date | 
| Phase 1: Forearm blood flow (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: Forearm blood flow (FBF) response to Sodium Nitroprusside (NTP) | FBF to NTP will me 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  11 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 me measured following the participants 8 week sleep intervention | t-PA release will be measured during Phase 2 at the participants visit 9 which is  11 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 1: FBF response to ACh+Vitamin C |  | FBF response to ACh+Vitamin C 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 me 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  11 weeks from their respective start date | 
| Phase 2: FBF response to ACh+Vitamin C | FBF to ACh+Vitamin C will me measured following the participants 8 week sleep intervention | FBF response to ACh+Vitamin C will be measured during Phase 2 at the participants visit 9 which is  11 weeks from their respective start date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep