HIV-1
Conditions
Keywords
Sleep
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.
Interventions
BEHAVIORALIndividualized Targeted Sleep
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.
Sponsors
University of Colorado, Boulder
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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 preceding 3-year period. * Pre- or peri-menopausal women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: FBF Response to ACh+Vitamin C | 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 | 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. |
| 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. | 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. |
| Phase 2: FBF Response to Acetylcholine (ACh) | FBF response to ACh will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date | FBF to ACh will be measured following the participants 8 week sleep intervention. |
| 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 response to NTP will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date | FBF to NTP will me measured following the participants 8 week sleep intervention |
| Phase 1: Endothelial Tissue Type Plasminogen Activator (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. | 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. |
| Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | t-PA release will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date | 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. |
| Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (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. | 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. |
| 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. | 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. |
| Phase 2: FBF Response to ACh+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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nightly Sleep Duration | Baseline | Nightly sleep duration was calculated as the weighted average of weeknights and weekend values \[(5 x weekday sleep duration)+(2 x weekend sleep duration)/7\]. |
Countries
United States
Participant flow
Pre-assignment details
Based on the participants nightly sleep duration they were enrolled either in Phase 1: No Intervention: Normal Sleep Group or Phase 1: No Intervention: Short Sleep Group. 10 participants with short nightly sleep duration were recruited separately and enrolled into Phase 2. After participants sign the informed consent, they complete a blood draw and a graded exercise stress test.
Participants by arm
| Arm | Count |
|---|---|
| No Intervention: Phase 1 Normal Sleep Group Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) 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). | 36 |
| No Intervention: Phase 1 Short Sleep Group Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) 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). | 42 |
| Experimental: Phase 2 Sleep Intervention Study Phase 2 is an intervention study designed to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night. | 10 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 4 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 2 |
Baseline characteristics
| Characteristic | No Intervention: Phase 1 Normal Sleep Group | No Intervention: Phase 1 Short Sleep Group | Experimental: Phase 2 Sleep Intervention Study | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 42 Participants | 10 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 37 Participants | 6 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 39 Participants | 10 Participants | 83 Participants |
| Region of Enrollment United States | 36 participants | 42 participants | 10 participants | 88 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 31 Participants | 36 Participants | 8 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 10 |
| other Total, other adverse events | 0 / 78 | 0 / 10 |
| serious Total, serious adverse events | 0 / 78 | 0 / 10 |
Outcome results
Primary
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.
Time frame: t-PA release will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Population: The number of participants analyzed is different than reported in the participant flow module due to the availability of BDK during the clinical trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | Saline | -0.8 ng/100 mL tissue/min | Standard Error 0.6 |
| Normal Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 12.5 | 20.9 ng/100 mL tissue/min | Standard Error 3.2 |
| Normal Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 25.0 | 33.3 ng/100 mL tissue/min | Standard Error 4.7 |
| Normal Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 50.0 | 53.5 ng/100 mL tissue/min | Standard Error 7.6 |
| Short Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 50.0 | 33.4 ng/100 mL tissue/min | Standard Error 4.1 |
| Short Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | Saline | -1.0 ng/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 25.0 | 23.8 ng/100 mL tissue/min | Standard Error 3.2 |
| Short Sleep Duration | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | BDK 12.5 | 11.4 ng/100 mL tissue/min | Standard Error 2.8 |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | Saline | 4.6 mL/100 mL tissue/min | Standard Error 0.3 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 4.0 | 11.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 8.0 | 12.4 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 16.0 | 14.1 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 4.0 | 9.2 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 8.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 16.0 | 12.1 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | Saline | 4.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 8.0 | 10.6 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 4.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 16.0 | 12.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 16.0 | 11.1 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 4.0 | 8.8 mL/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | Saline | 3.3 mL/100 mL tissue/min | Standard Error 0.2 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | ACh 8.0 | 9.6 mL/100 mL tissue/min | Standard Error 0.6 |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Saline | 4.6 mL/100 mL tissue/min | Standard Error 0.3 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 4.0 | 11.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 8.0 | 12.4 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 16.0 | 14.1 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 4.0 | 14.3 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 8.0 | 15.2 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Ach 16.0 | 16.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: FBF Response to ACh+Vitamin C | Saline | 5.1 mL/100 mL tissue/min | Standard Error 0.4 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Vitamin C | Ach 8.0 | 10.5 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Vitamin C | Ach 4.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Vitamin C | Ach 16.0 | 12.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh) | Phase 1: FBF Response to ACh+Vitamin C | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Vitamin C | Ach 16.0 | 15.9 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Vitamin C | Ach 4.0 | 13.3 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Vitamin C | Saline | 4.4 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 1: FBF Response to ACh+Vitamin C | Ach 8.0 | 14.0 mL/100 mL tissue/min | Standard Error 0.7 |
Primary
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.
Time frame: FBF response to ACh will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Population: The number or participants analyzed is different than the participant flow module as these are the participants who completed visit 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | Saline | 4.6 mL/100 mL tissue/min | Standard Error 0.3 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 4.0 | 11.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 8.0 | 12.4 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 16.0 | 14.1 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 16.0 | 12.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 8.0 | 10.5 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | ACh 4.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.5 |
Primary
Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)
Time frame: FBF response to NTP will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.
Population: The number or participants analyzed is different than the participant flow module due to availability of Sodium Nitroprusside.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | Saline | 4.8 mL/100 mL tissue/min | Standard Error 0.4 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 1.0 | 13.9 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 2.0 | 16.1 mL/100 mL tissue/min | Standard Error 1 |
| Normal Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 4.0 | 17.0 mL/100 mL tissue/min | Standard Error 1.1 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 4.0 | 16.7 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | Saline | 4.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 2.0 | 14.5 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 1.0 | 12.4 mL/100 mL tissue/min | Standard Error 0.8 |
Primary
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.
Time frame: t-PA release will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | Saline | -1.8 ng/100 mL tissue/min | Standard Error 1.8 |
| Normal Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 12.5 | 15.1 ng/100 mL tissue/min | Standard Error 7.1 |
| Normal Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 25.0 | 20.6 ng/100 mL tissue/min | Standard Error 6.3 |
| Normal Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 50.0 | 38.9 ng/100 mL tissue/min | Standard Error 8.4 |
| Short Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 50.0 | 78.8 ng/100 mL tissue/min | Standard Error 16.6 |
| Short Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | Saline | -2.1 ng/100 mL tissue/min | Standard Error 2.5 |
| Short Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 25.0 | 50.1 ng/100 mL tissue/min | Standard Error 14.6 |
| Short Sleep Duration | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | BDK 12.5 | 25.4 ng/100 mL tissue/min | Standard Error 5.8 |
Primary
Phase 2: FBF Response to Acetylcholine (ACh)
FBF to ACh will be measured following the participants 8 week sleep intervention.
Time frame: FBF response to ACh will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.4 |
| Normal Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | ACh 4.0 | 9.2 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Ach 8.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Ach 16.0 | 11.3 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Ach 16.0 | 14.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Saline | 4.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | Ach 8.0 | 12.2 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration | Phase 2: FBF Response to Acetylcholine (ACh) | ACh 4.0 | 11.1 mL/100 mL tissue/min | Standard Error 0.7 |
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.4 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 4.0 | 9.2 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 8.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 16.0 | 11.3 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 4.0 | 9.0 mL/100 mL tissue/min | Standard Error 0.8 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 8.0 | 9.7 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | ACh 16.0 | 10.8 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+L-NMMA | Saline | 3.3 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+L-NMMA | ACh 8.0 | 12.2 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+L-NMMA | ACh 4.0 | 11.1 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+L-NMMA | ACh 16.0 | 14.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+L-NMMA | Saline | 4.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+L-NMMA | ACh 16.0 | 10.8 mL/100 mL tissue/min | Standard Error 1 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+L-NMMA | ACh 4.0 | 7.6 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+L-NMMA | Saline | 3.8 mL/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+L-NMMA | ACh 8.0 | 10.1 mL/100 mL tissue/min | Standard Error 1.1 |
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 16.0 | 11.3 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 4.0 | 9.2 mL/100 mL tissue/min | Standard Error 0.8 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.4 |
| Normal Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 8.0 | 9.9 mL/100 mL tissue/min | Standard Error 0.9 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 4.0 | 12.6 mL/100 mL tissue/min | Standard Error 1.3 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 8.0 | 13.5 mL/100 mL tissue/min | Standard Error 1.3 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | Saline | 4.3 mL/100 mL tissue/min | Standard Error 0.5 |
| Short Sleep Duration | Phase 2: FBF Response to ACh+Vitamin C | ACh 16.0 | 14.8 mL/100 mL tissue/min | Standard Error 1.5 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+Vitamin C | Saline | 4.0 mL/100 mL tissue/min | Standard Error 0.3 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+Vitamin C | ACh 4.0 | 11.1 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+Vitamin C | ACh 8.0 | 12.2 mL/100 mL tissue/min | Standard Error 0.7 |
| Short Sleep Duration (ACh) | Phase 2: FBF Response to ACh+Vitamin C | ACh 16.0 | 14.0 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+Vitamin C | ACh 4.0 | 12.4 mL/100 mL tissue/min | Standard Error 1.7 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+Vitamin C | Saline | 4.8 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+Vitamin C | ACh 16.0 | 14.2 mL/100 mL tissue/min | Standard Error 1.5 |
| Short Sleep Duration (ACh+L-NMMA) | Phase 2: FBF Response to ACh+Vitamin C | ACh 8.0 | 13.0 mL/100 mL tissue/min | Standard Error 1.5 |
Primary
Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)
FBF to NTP will me measured following the participants 8 week sleep intervention
Time frame: FBF response to NTP will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | Saline | 3.6 mL/100 mL tissue/min | Standard Error 0.4 |
| Normal Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 1.0 | 12.0 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 2.0 | 13.9 mL/100 mL tissue/min | Standard Error 0.9 |
| Normal Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 4.0 | 15.7 mL/100 mL tissue/min | Standard Error 1.1 |
| Short Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 4.0 | 15.7 mL/100 mL tissue/min | Standard Error 1.4 |
| Short Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | Saline | 4.2 mL/100 mL tissue/min | Standard Error 0.6 |
| Short Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 2.0 | 14.6 mL/100 mL tissue/min | Standard Error 1.2 |
| Short Sleep Duration | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | NTP 1.0 | 13.8 mL/100 mL tissue/min | Standard Error 1.1 |
Secondary
Nightly Sleep Duration
Nightly sleep duration was calculated as the weighted average of weeknights and weekend values \[(5 x weekday sleep duration)+(2 x weekend sleep duration)/7\].
Time frame: Baseline
Population: Nightly sleep duration was measured during Phase 1 at the participants initial visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Sleep Duration | Nightly Sleep Duration | 7.8 hours/night | Standard Error 0.2 |
| Short Sleep Duration | Nightly Sleep Duration | 5.8 hours/night | Standard Error 0.2 |