Trial Outcomes & Findings for Study of Cardiovascular Disease and Obstructive Sleep Apnea (NCT NCT01637623)
NCT ID: NCT01637623
Last Updated: 2020-08-14
Results Overview
The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
87 participants
Primary outcome timeframe
baseline and 6 weeks
Results posted on
2020-08-14
Participant Flow
Participant milestones
| Measure |
Losartan
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
29
|
30
|
28
|
|
Overall Study
Received Intervention
|
28
|
30
|
27
|
|
Overall Study
Did Not Receive Intervention
|
1
|
0
|
1
|
|
Overall Study
Analyzed
|
28
|
30
|
28
|
|
Overall Study
COMPLETED
|
28
|
30
|
25
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
3
|
Reasons for withdrawal
| Measure |
Losartan
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
2
|
|
Overall Study
Physician Decision
|
1
|
0
|
1
|
Baseline Characteristics
Study of Cardiovascular Disease and Obstructive Sleep Apnea
Baseline characteristics by cohort
| Measure |
Losartan
n=28 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=30 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=28 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49 years
STANDARD_DEVIATION 12 • n=93 Participants
|
49 years
STANDARD_DEVIATION 8 • n=4 Participants
|
47 years
STANDARD_DEVIATION 9 • n=27 Participants
|
49 years
STANDARD_DEVIATION 10 • n=483 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
34 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
52 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=93 Participants
|
27 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
78 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
79 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=93 Participants
|
30 participants
n=4 Participants
|
28 participants
n=27 Participants
|
86 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: baseline and 6 weeksPopulation: Data is for fewer subjects than were randomized to treatment because a useable nerve signal was not obtained on all participants.
The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.
Outcome measures
| Measure |
Losartan
n=18 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=23 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=25 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
Baseline
|
-0.54 bursts/minute*%SaO2
Standard Deviation 0.29
|
-0.84 bursts/minute*%SaO2
Standard Deviation 0.47
|
-0.71 bursts/minute*%SaO2
Standard Deviation 0.43
|
|
Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
Following 6 weeks of therapy
|
-0.69 bursts/minute*%SaO2
Standard Deviation .50
|
-0.66 bursts/minute*%SaO2
Standard Deviation 0.38
|
-0.61 bursts/minute*%SaO2
Standard Deviation 0.40
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: Since this was a secondary outcome measure, not all participants were able to undergo this procedure since scheduling did not always allow with scheduling for primary outcome measure.
measurement of vascular stiffness assessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=19 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=20 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=18 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Change in Aortic Pulse Wave Velocity
|
-0.6 m/s
Interval -1.0 to -0.2
|
-0.03 m/s
Interval -0.5 to 0.4
|
0.2 m/s
Interval -0.3 to 0.7
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: Since this was a secondary outcome measure, not all participants were able to undergo this procedure since scheduling did not always allow with scheduling for primary outcome measure.
Assessment measures of cerebral blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Cerebrovascular conductance (CVC) was calculated as velocity-time integral/mean arterial pressure.
Outcome measures
| Measure |
Losartan
n=20 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=20 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=22 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Cerebrovascular Conductance
baseline
|
0.32 cm/sec/mmHg
Standard Deviation 0.13
|
0.27 cm/sec/mmHg
Standard Deviation 0.97
|
0.33 cm/sec/mmHg
Standard Deviation 0.11
|
|
Cerebrovascular Conductance
After six weeks treatment
|
0.36 cm/sec/mmHg
Standard Deviation 0.14
|
0.31 cm/sec/mmHg
Standard Deviation 0.12
|
0.34 cm/sec/mmHg
Standard Deviation 0.12
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: Participants were not able to conduct all procedures due to scheduling and on occasion, difficulty obtaining a signal. Prioritization of primary outcome measure was the goal.
Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.
Outcome measures
| Measure |
Losartan
n=26 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=30 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=27 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Forearm Vascular Conductance
baseline
|
0.41 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.21
|
0.43 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.2
|
0.49 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.31
|
|
Forearm Vascular Conductance
After 6 weeks of treatment
|
0.42 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.17
|
0.55 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.31
|
0.51 ml/min^-1 dL^-1 mmHg^-1
Standard Deviation 0.29
|
SECONDARY outcome
Timeframe: baseline and 6 weeksassessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=28 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=30 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=28 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Change in Minute Ventilation at Normoxia
baseline - normoxia in L/min
|
8.9 normoxia - L/min
Standard Deviation 1.7
|
9.3 normoxia - L/min
Standard Deviation 2.1
|
9.3 normoxia - L/min
Standard Deviation 2.1
|
|
Change in Minute Ventilation at Normoxia
six weeks - normoxia in L/min
|
8.9 normoxia - L/min
Standard Deviation 2.1
|
9.8 normoxia - L/min
Standard Deviation 2.6
|
8.8 normoxia - L/min
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: baseline and 6 weeksassessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=28 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=30 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=28 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Change in Minute Ventilation During Hypoxia
hypoxia - baseline in L/min*PERCENTSaO2
|
-0.41 hypoxia - L/min*%SaO2
Standard Deviation 0.28
|
-0.53 hypoxia - L/min*%SaO2
Standard Deviation 0.41
|
-0.44 hypoxia - L/min*%SaO2
Standard Deviation 0.29
|
|
Change in Minute Ventilation During Hypoxia
hypoxia - after six weeks treatment in L/min*%SaO2
|
-0.37 hypoxia - L/min*%SaO2
Standard Deviation 0.25
|
-0.43 hypoxia - L/min*%SaO2
Standard Deviation 0.37
|
-0.48 hypoxia - L/min*%SaO2
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: The number of participants differ between outcome measures due to difficulty in obtaining a viable signal for one outcome vs another and based on scheduling to prioritize the primary outcome measure.
assessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=17 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=19 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=14 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Aortic Augmentation Index
baseline
|
17.3 PERCENT of the pulse pressure
Interval 12.7 to 22.0
|
18.8 PERCENT of the pulse pressure
Interval 14.5 to 23.1
|
21.5 PERCENT of the pulse pressure
Interval 16.8 to 26.3
|
|
Aortic Augmentation Index
following six weeks of therapy
|
16.1 PERCENT of the pulse pressure
Interval 11.4 to 20.7
|
16.7 PERCENT of the pulse pressure
Interval 12.5 to 21.0
|
22.5 PERCENT of the pulse pressure
Interval 17.7 to 27.2
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.
Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=17 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=19 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=14 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Mean Change in PERCENT Vasodilation
|
1.38 % change in Max relative FMD
Interval 0.19 to 2.57
|
0.18 % change in Max relative FMD
Interval -0.97 to 1.32
|
-1.06 % change in Max relative FMD
Interval -2.28 to 0.16
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.
Severity of sleep apnea assessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=28 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=28 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=26 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Apnea-Hypopnea Index
baseline
|
46 events/hour
Interval 27.0 to 58.0
|
33 events/hour
Interval 24.0 to 50.0
|
35 events/hour
Interval 18.0 to 59.0
|
|
Apnea-Hypopnea Index
after six weeks of treatment
|
44 events/hour
Interval 25.0 to 67.0
|
45 events/hour
Interval 22.0 to 68.0
|
26 events/hour
Interval 15.0 to 62.0
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.
assessed before and after study drug treatment
Outcome measures
| Measure |
Losartan
n=28 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=28 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=26 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
baseline
|
10 percentage of total sleep time
Interval 4.0 to 25.0
|
5 percentage of total sleep time
Interval 1.0 to 15.0
|
5 percentage of total sleep time
Interval 1.0 to 9.0
|
|
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
following six weeks of therapy
|
12 percentage of total sleep time
Interval 2.0 to 35.0
|
8 percentage of total sleep time
Interval 2.0 to 18.0
|
3 percentage of total sleep time
Interval 1.0 to 8.0
|
SECONDARY outcome
Timeframe: baseline and 6 weeksPopulation: The number of participants differ between primary and secondary outcome variables due to occasional inability to obtain a viable signal for the variable and due to scheduling difficulties and prioritizing the primary outcome measure.
Change in mean 24 hour blood pressure (mean arterial pressure)
Outcome measures
| Measure |
Losartan
n=23 Participants
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Losartan: Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.
|
Allopurinol
n=25 Participants
Allopurinol 300 mg daily for 6 weeks
Allopurinol: Allopurinol 300 mg daily for 6 weeks
|
Placebo
n=20 Participants
Placebo capsule daily for 6 weeks
Placebo: Placebo capsule daily for 6 weeks
|
|---|---|---|---|
|
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
|
-4.73 mm Hg
Interval -7.67 to -1.79
|
-2.58 mm Hg
Interval -5.51 to 0.34
|
1.02 mm Hg
Interval -2.2 to 4.25
|
Adverse Events
Losartan
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Allopurinol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
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
John M. Dopp
University of Wisconsin School of Pharmacy
Phone: 608-265-9352
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place