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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL105365 | U.S. NIH Grant/Contract | View source | |
| A561000 | Other Identifier | UW, Madison | |
| PHARM/PHARMACY/PHARMACY | Other Identifier | UW, Madison |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The purpose of this study is to determine if two medicines (allopurinol and losartan) can influence heart and blood vessel health compared to placebo in patients with sleep apnea who are using continuous positive airway pressure (CPAP).
The specific aims of this research project are: 1) Determine if treatment with losartan, an angiotensin type I receptor (AT1R) antagonist, or allopurinol, a XO inhibitor, normalize chemoreflex control of sympathetic outflow and ventilation and improve local vascular regulation and stiffness; and 2) Determine if these interventions reduce the severity of sleep disordered breathing and lower diurnal blood pressure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losartan | Active Comparator | Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. |
|
| Allopurinol | Active Comparator | Allopurinol 300 mg daily for 6 weeks |
|
| Placebo | Placebo Comparator | Placebo capsule daily for 6 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia | 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. | baseline and 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Aortic Pulse Wave Velocity | measurement of vascular stiffness assessed before and after study drug treatment | baseline and 6 weeks |
| Cerebrovascular Conductance | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Dopp, Pharm.D. | UW Madison School of Pharmacy | Principal Investigator |
| Barbara J Morgan, PhD, PT | UW Madison School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aurora Bay Care | Green Bay | Wisconsin | 54308 | United States | ||
| Gundersen Lutheran |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29750475 | Result | Morgan BJ, Teodorescu M, Pegelow DF, Jackson ER, Schneider DL, Plante DT, Gapinski JP, Hetzel SJ, Dopp JM. Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea. Exp Physiol. 2018 Jul;103(7):941-955. doi: 10.1113/EP087006. Epub 2018 Jun 8. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Allopurinol | Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks |
| FG002 | Placebo | Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
baseline analysis population includes data for those participants that were analyzed, per the participant flow
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia | 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. | Data is for fewer subjects than were randomized to treatment because a useable nerve signal was not obtained on all participants. | Posted | Mean | Standard Deviation | bursts/minute*%SaO2 | baseline and 6 weeks |
|
Up to 6 weeks
Adverse Events Data reported for all participants who started the study, per participant flow.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John M. Dopp | University of Wisconsin School of Pharmacy | 608-265-9352 | john.dopp@wisc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 25, 2017 | Jan 29, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D006973 | Hypertension |
| D012891 | Sleep Apnea Syndromes |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Allopurinol | Drug | Allopurinol 300 mg daily for 6 weeks |
|
| Placebo | Drug | Placebo capsule daily for 6 weeks |
|
| baseline and 6 weeks |
| Forearm Vascular Conductance | Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment. | baseline and 6 weeks |
| Change in Minute Ventilation at Normoxia | assessed before and after study drug treatment | baseline and 6 weeks |
| Change in Minute Ventilation During Hypoxia | assessed before and after study drug treatment | baseline and 6 weeks |
| Aortic Augmentation Index | assessed before and after study drug treatment | baseline and 6 weeks |
| Mean Change in PERCENT Vasodilation | Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment | baseline and 6 weeks |
| Apnea-Hypopnea Index | Severity of sleep apnea assessed before and after study drug treatment | baseline and 6 weeks |
| PERCENT Time Spent Below 88 PERCENT Oxygen Saturation | assessed before and after study drug treatment | baseline and 6 weeks |
| Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure) | Change in mean 24 hour blood pressure (mean arterial pressure) | baseline and 6 weeks |
| La Crosse |
| Wisconsin |
| 54601 |
| United States |
| University of Wisconsin Madison | Madison | Wisconsin | 53705 | United States |
| Marshfield Clinic | Marshfield | Wisconsin | 54449 | United States |
| Allopurinol |
Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks |
| BG002 | Placebo | Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Allopurinol |
Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks |
| OG002 | Placebo | Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks |
|
|
| Secondary | Change in Aortic Pulse Wave Velocity | measurement of vascular stiffness assessed before and after study drug treatment | 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. | Posted | Mean | 95% Confidence Interval | m/s | baseline and 6 weeks |
|
|
|
| Secondary | Cerebrovascular Conductance | 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. | 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. | Posted | Mean | Standard Deviation | cm/sec/mmHg | baseline and 6 weeks |
|
|
|
| Secondary | Forearm Vascular Conductance | Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment. | 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. | Posted | Mean | Standard Deviation | ml/min^-1 dL^-1 mmHg^-1 | baseline and 6 weeks |
|
|
|
| Secondary | Change in Minute Ventilation at Normoxia | assessed before and after study drug treatment | Posted | Mean | Standard Deviation | normoxia - L/min | baseline and 6 weeks |
|
|
|
| Secondary | Change in Minute Ventilation During Hypoxia | assessed before and after study drug treatment | Posted | Mean | Standard Deviation | hypoxia - L/min*%SaO2 | baseline and 6 weeks |
|
|
|
| Secondary | Aortic Augmentation Index | assessed before and after study drug treatment | 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. | Posted | Mean | 95% Confidence Interval | PERCENT of the pulse pressure | baseline and 6 weeks |
|
|
|
| Secondary | Mean Change in PERCENT Vasodilation | Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment | 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. | Posted | Mean | 95% Confidence Interval | % change in Max relative FMD | baseline and 6 weeks |
|
|
|
| Secondary | Apnea-Hypopnea Index | Severity of sleep apnea assessed before and after study drug treatment | 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. | Posted | Median | Inter-Quartile Range | events/hour | baseline and 6 weeks |
|
|
|
| Secondary | PERCENT Time Spent Below 88 PERCENT Oxygen Saturation | assessed before and after study drug treatment | 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. | Posted | Median | Inter-Quartile Range | percentage of total sleep time | baseline and 6 weeks |
|
|
|
| Secondary | Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure) | Change in mean 24 hour blood pressure (mean arterial pressure) | 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. | Posted | Mean | 95% Confidence Interval | mm Hg | baseline and 6 weeks |
|
|
|
| 0 |
| 29 |
| 0 |
| 29 |
| 0 |
| 29 |
| EG001 | Allopurinol | Allopurinol 300 mg daily for 6 weeks Allopurinol: Allopurinol 300 mg daily for 6 weeks | 0 | 30 | 0 | 30 | 0 | 30 |
| EG002 | Placebo | Placebo capsule daily for 6 weeks Placebo: Placebo capsule daily for 6 weeks | 0 | 28 | 0 | 28 | 0 | 28 |
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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