HIV-1, Insufficient Sleep and Vascular Endothelial Dysfunction

NCT04956861 | Completed Results DMC

• 1 other identifier: 150465
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1

Keywords

Sleep

Outcome Measures

Primary Outcomes (10)

• Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)

  FBF was measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min; the doses of Acetylcholine infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose were measured and the mean value reported. Values after saline and after ACh 4.0, 8.0 and 16.0 at week 3 are reported.

  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 ~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 Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK)

  Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells.

  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. Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x \[101-hematocrit/100\]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells.

  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+Ng-monomethyl-L-arginine (L-NMMA)

  To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of 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

  After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated.

  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. To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of L-NMMA.

  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. After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated.

  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

Secondary Outcomes (1)

• Nightly Sleep Duration

  Baseline

Study Arms (2)

Phase 1

NO INTERVENTION

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).

Phase 2

EXPERIMENTAL

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

Interventions

Individualized Targeted Sleep BEHAVIORAL

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.

Phase 2

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Receiving hormone replacement therapy (HRT) currently or in the preceding 3-year period.
• Pre- or peri-menopausal women

Sponsors & Collaborators

• University of Colorado, Boulder: lead

Study Sites (1)

UC-Boulder Clinical and Translational Research Center

Boulder, Colorado, 80309, United States

Location

Results Point of Contact

• Title: Christopher DeSouza Ph.D.
• Organization: University of Colorado

desouzac@colorado.edu

303-492-2988

Study Officials

• Christopher DeSouza, PhD

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 9, 2021
• Study Start: December 17, 2015
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: January 23, 2025
• Results First Posted: January 23, 2025

Record last verified: 2024-12

Locations

US (1)