Trial Outcomes & Findings for HIV-1, Insufficient Sleep and Vascular Endothelial Dysfunction (NCT NCT04956861)

NCT ID: NCT04956861

Last Updated: 2025-01-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

88 participants

Primary outcome timeframe

FBF response to ACh will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date.

Results posted on

2025-01-23

Participant Flow

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.

Participant milestones

Participant milestones
Measure
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).
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).
Experimental: Phase 2
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. .
Overall Study
STARTED
36
42
10
Overall Study
COMPLETED
28
33
7
Overall Study
NOT COMPLETED
8
9
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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).
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).
Experimental: Phase 2
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. .
Overall Study
Withdrawal by Subject
4
4
2
Overall Study
Physician Decision
4
5
1

Baseline Characteristics

HIV-1, Insufficient Sleep and Vascular Endothelial Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
No Intervention: Phase 1 Normal Sleep Group
n=36 Participants
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).
No Intervention: Phase 1 Short Sleep Group
n=42 Participants
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).
Experimental: Phase 2 Sleep Intervention Study
n=10 Participants
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.
Total
n=88 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Age, Categorical
Between 18 and 65 years
36 Participants
n=5 Participants
42 Participants
n=7 Participants
10 Participants
n=5 Participants
88 Participants
n=4 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
6 Participants
n=7 Participants
2 Participants
n=5 Participants
13 Participants
n=4 Participants
Sex: Female, Male
Male
31 Participants
n=5 Participants
36 Participants
n=7 Participants
8 Participants
n=5 Participants
75 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants
n=5 Participants
5 Participants
n=7 Participants
4 Participants
n=5 Participants
14 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
31 Participants
n=5 Participants
37 Participants
n=7 Participants
6 Participants
n=5 Participants
74 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=5 Participants
2 Participants
n=7 Participants
0 Participants
n=5 Participants
4 Participants
n=4 Participants
Race (NIH/OMB)
White
34 Participants
n=5 Participants
39 Participants
n=7 Participants
10 Participants
n=5 Participants
83 Participants
n=4 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Region of Enrollment
United States
36 participants
n=5 Participants
42 participants
n=7 Participants
10 participants
n=5 Participants
88 participants
n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=18 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=22 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)
Saline
4.6 mL/100 mL tissue/min
Standard Error 0.3
4.2 mL/100 mL tissue/min
Standard Error 0.3
Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)
ACh 4.0
11.7 mL/100 mL tissue/min
Standard Error 0.8
9.9 mL/100 mL tissue/min
Standard Error 0.5
Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)
ACh 8.0
12.4 mL/100 mL tissue/min
Standard Error 0.8
10.5 mL/100 mL tissue/min
Standard Error 0.6
Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh)
ACh 16.0
14.1 mL/100 mL tissue/min
Standard Error 0.7
12.0 mL/100 mL tissue/min
Standard Error 0.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=7 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=7 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 2: FBF Response to Acetylcholine (ACh)
Saline
4.2 mL/100 mL tissue/min
Standard Error 0.4
4.0 mL/100 mL tissue/min
Standard Error 0.3
Phase 2: FBF Response to Acetylcholine (ACh)
ACh 4.0
9.2 mL/100 mL tissue/min
Standard Error 0.8
11.1 mL/100 mL tissue/min
Standard Error 0.7
Phase 2: FBF Response to Acetylcholine (ACh)
Ach 8.0
9.9 mL/100 mL tissue/min
Standard Error 0.9
12.2 mL/100 mL tissue/min
Standard Error 0.7
Phase 2: FBF Response to Acetylcholine (ACh)
Ach 16.0
11.3 mL/100 mL tissue/min
Standard Error 0.9
14.0 mL/100 mL tissue/min
Standard Error 0.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=18 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=22 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
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
12.4 mL/100 mL tissue/min
Standard Error 0.8
Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)
NTP 2.0
16.1 mL/100 mL tissue/min
Standard Error 1.0
14.5 mL/100 mL tissue/min
Standard Error 0.7
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
16.7 mL/100 mL tissue/min
Standard Error 0.8
Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)
Saline
4.8 mL/100 mL tissue/min
Standard Error 0.4
4.0 mL/100 mL tissue/min
Standard Error 0.3

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=7 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=7 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP)
Saline
3.6 mL/100 mL tissue/min
Standard Error 0.4
4.2 mL/100 mL tissue/min
Standard Error 0.6
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
13.8 mL/100 mL tissue/min
Standard Error 1.1
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
14.6 mL/100 mL tissue/min
Standard Error 1.2
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
15.7 mL/100 mL tissue/min
Standard Error 1.4

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=16 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=14 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
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
-1.0 ng/100 mL tissue/min
Standard Error 0.5
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
11.4 ng/100 mL tissue/min
Standard Error 2.8
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
23.8 ng/100 mL tissue/min
Standard Error 3.2
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
33.4 ng/100 mL tissue/min
Standard Error 4.1

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=5 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=5 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
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
25.4 ng/100 mL tissue/min
Standard Error 5.8
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
50.1 ng/100 mL tissue/min
Standard Error 14.6
Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK)
Saline
-1.8 ng/100 mL tissue/min
Standard Error 1.8
-2.1 ng/100 mL tissue/min
Standard Error 2.5
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
78.8 ng/100 mL tissue/min
Standard Error 16.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=18 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=18 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
n=22 Participants
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
n=22 Participants
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
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
12.1 mL/100 mL tissue/min
Standard Error 0.8
12.0 mL/100 mL tissue/min
Standard Error 0.6
11.1 mL/100 mL tissue/min
Standard Error 0.6
Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA)
Saline
4.6 mL/100 mL tissue/min
Standard Error 0.3
4.0 mL/100 mL tissue/min
Standard Error 0.3
4.2 mL/100 mL tissue/min
Standard Error 0.3
3.3 mL/100 mL tissue/min
Standard Error 0.2
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
9.2 mL/100 mL tissue/min
Standard Error 0.8
9.9 mL/100 mL tissue/min
Standard Error 0.5
8.8 mL/100 mL tissue/min
Standard Error 0.5
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
9.9 mL/100 mL tissue/min
Standard Error 0.8
10.6 mL/100 mL tissue/min
Standard Error 0.6
9.6 mL/100 mL tissue/min
Standard Error 0.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=18 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=18 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
n=22 Participants
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
n=22 Participants
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 1: FBF Response to ACh+Vitamin C
Saline
4.6 mL/100 mL tissue/min
Standard Error 0.3
5.1 mL/100 mL tissue/min
Standard Error 0.4
4.2 mL/100 mL tissue/min
Standard Error 0.3
4.4 mL/100 mL tissue/min
Standard Error 0.3
Phase 1: FBF Response to ACh+Vitamin C
Ach 4.0
11.7 mL/100 mL tissue/min
Standard Error 0.8
14.3 mL/100 mL tissue/min
Standard Error 0.9
9.9 mL/100 mL tissue/min
Standard Error 0.5
13.3 mL/100 mL tissue/min
Standard Error 0.6
Phase 1: FBF Response to ACh+Vitamin C
Ach 8.0
12.4 mL/100 mL tissue/min
Standard Error 0.8
15.2 mL/100 mL tissue/min
Standard Error 0.8
10.5 mL/100 mL tissue/min
Standard Error 0.6
14.0 mL/100 mL tissue/min
Standard Error 0.7
Phase 1: FBF Response to ACh+Vitamin C
Ach 16.0
14.1 mL/100 mL tissue/min
Standard Error 0.7
16.7 mL/100 mL tissue/min
Standard Error 0.8
12.0 mL/100 mL tissue/min
Standard Error 0.6
15.9 mL/100 mL tissue/min
Standard Error 0.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=7 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=7 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
n=7 Participants
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
n=7 Participants
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 2: FBF Response to ACh+L-NMMA
Saline
4.2 mL/100 mL tissue/min
Standard Error 0.4
3.3 mL/100 mL tissue/min
Standard Error 0.3
4.0 mL/100 mL tissue/min
Standard Error 0.3
3.8 mL/100 mL tissue/min
Standard Error 0.5
Phase 2: FBF Response to ACh+L-NMMA
ACh 4.0
9.2 mL/100 mL tissue/min
Standard Error 0.8
9.0 mL/100 mL tissue/min
Standard Error 0.8
11.1 mL/100 mL tissue/min
Standard Error 0.7
7.6 mL/100 mL tissue/min
Standard Error 0.6
Phase 2: FBF Response to ACh+L-NMMA
ACh 16.0
11.3 mL/100 mL tissue/min
Standard Error 0.9
10.8 mL/100 mL tissue/min
Standard Error 0.9
14.0 mL/100 mL tissue/min
Standard Error 0.6
10.8 mL/100 mL tissue/min
Standard Error 1.0
Phase 2: FBF Response to ACh+L-NMMA
ACh 8.0
9.9 mL/100 mL tissue/min
Standard Error 0.9
9.7 mL/100 mL tissue/min
Standard Error 0.9
12.2 mL/100 mL tissue/min
Standard Error 0.7
10.1 mL/100 mL tissue/min
Standard Error 1.1

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=7 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=7 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
n=7 Participants
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
n=7 Participants
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Phase 2: FBF Response to ACh+Vitamin C
ACh 4.0
9.2 mL/100 mL tissue/min
Standard Error 0.8
12.6 mL/100 mL tissue/min
Standard Error 1.3
11.1 mL/100 mL tissue/min
Standard Error 0.7
12.4 mL/100 mL tissue/min
Standard Error 1.7
Phase 2: FBF Response to ACh+Vitamin C
ACh 8.0
9.9 mL/100 mL tissue/min
Standard Error 0.9
13.5 mL/100 mL tissue/min
Standard Error 1.3
12.2 mL/100 mL tissue/min
Standard Error 0.7
13.0 mL/100 mL tissue/min
Standard Error 1.5
Phase 2: FBF Response to ACh+Vitamin C
Saline
4.2 mL/100 mL tissue/min
Standard Error 0.4
4.3 mL/100 mL tissue/min
Standard Error 0.5
4.0 mL/100 mL tissue/min
Standard Error 0.3
4.8 mL/100 mL tissue/min
Standard Error 0.6
Phase 2: FBF Response to ACh+Vitamin C
ACh 16.0
11.3 mL/100 mL tissue/min
Standard Error 0.9
14.8 mL/100 mL tissue/min
Standard Error 1.5
14.0 mL/100 mL tissue/min
Standard Error 0.6
14.2 mL/100 mL tissue/min
Standard Error 1.5

SECONDARY outcome

Timeframe: Baseline

Population: Nightly sleep duration was measured during Phase 1 at the participants initial visit.

Nightly sleep duration was calculated as the weighted average of weeknights and weekend values \[(5 x weekday sleep duration)+(2 x weekend sleep duration)/7\].

Outcome measures

Outcome measures
Measure
Normal Sleep Duration
n=30 Participants
Normal Sleep Duration group slept \>7 h/night.
Short Sleep Duration
n=38 Participants
Short Sleep Duration group slept \<7h/night.
Short Sleep Duration (ACh)
Short Sleep Duration group slept \<7h/night. Forearm blood flow (FBF) measured in response to Acetylcholine.
Short Sleep Duration (ACh+L-NMMA)
Short Sleep Duration group slept \<7h/night. FBF measured in response to Acetylcholine+L-NMMA.
Nightly Sleep Duration
7.8 hours/night
Standard Error 0.2
5.8 hours/night
Standard Error 0.2

Adverse Events

Phase 1: Cross-sectional Study

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Phase 2: Intervention Study

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Christopher DeSouza Ph.D.

University of Colorado

Phone: 303-492-2988

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place