Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea

David W. Carley; Bharati Prasad; Kathryn J. Reid; Roneil Malkani; Hryar Attarian; Sabra M. Abbott; Boris Vern; Hui Xie; Chengbo Yuan; Phyllis C. Zee

doi:10.1093/sleep/zsx184

Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea

David W. Carley^*, Bharati Prasad, Kathryn J. Reid, Roneil Malkani, Hryar Attarian, Sabra M. Abbott, Boris Vern, Hui Xie, Chengbo Yuan, Phyllis C. Zee

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

106 Scopus citations

Abstract

Study Objectives: There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. Methods: By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. Results: At baseline, overall apnea–hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m², and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by ?3.8 ± 0.8 points from baseline (p < .0001) and by ?2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. Conclusions: These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.

Original language	English (US)
Article number	Y
Journal	Sleep
Volume	41
Issue number	1
DOIs	https://doi.org/10.1093/sleep/zsx184
State	Published - Jan 1 2018

Funding

The authors gratefully acknowledge technical support provided by Julie Law, Kaitlyn Jeffries, Henry Arantes, Rosemary Ortiz, Gary Pearson, Natalie Pace, and James Sbarboro. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Heart Lung and Blood Institute Grant Number UM1HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1-HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1- HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003.

Keywords

Cannabinoid
Clinical trial
Obstructive sleep apnea
Pharmacotherapy

ASJC Scopus subject areas

General Medicine

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10.1093/sleep/zsx184

Cite this

@article{2398f5cd9400463787bcb118615bf93c,

title = "Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea",

abstract = "Study Objectives: There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. Methods: By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. Results: At baseline, overall apnea–hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m2, and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by ?3.8 ± 0.8 points from baseline (p < .0001) and by ?2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. Conclusions: These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.",

keywords = "Cannabinoid, Clinical trial, Obstructive sleep apnea, Pharmacotherapy",

author = "Carley, {David W.} and Bharati Prasad and Reid, {Kathryn J.} and Roneil Malkani and Hryar Attarian and Abbott, {Sabra M.} and Boris Vern and Hui Xie and Chengbo Yuan and Zee, {Phyllis C.}",

note = "Funding Information: The authors gratefully acknowledge technical support provided by Julie Law, Kaitlyn Jeffries, Henry Arantes, Rosemary Ortiz, Gary Pearson, Natalie Pace, and James Sbarboro. Research reported in this publication was supported, in part, by the National Institutes of Health{\textquoteright}s National Heart Lung and Blood Institute Grant Number UM1HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1-HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. Funding Information: This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1- HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003.",

year = "2018",

month = jan,

day = "1",

doi = "10.1093/sleep/zsx184",

language = "English (US)",

volume = "41",

journal = "Sleep",

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number = "1",

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TY - JOUR

T1 - Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial

T2 - Effects of dronabinol in obstructive sleep apnea

AU - Carley, David W.

AU - Prasad, Bharati

AU - Reid, Kathryn J.

AU - Malkani, Roneil

AU - Attarian, Hryar

AU - Abbott, Sabra M.

AU - Vern, Boris

AU - Xie, Hui

AU - Yuan, Chengbo

AU - Zee, Phyllis C.

N1 - Funding Information: The authors gratefully acknowledge technical support provided by Julie Law, Kaitlyn Jeffries, Henry Arantes, Rosemary Ortiz, Gary Pearson, Natalie Pace, and James Sbarboro. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Heart Lung and Blood Institute Grant Number UM1HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1-HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003. Funding Information: This study was funded by National Institutes of Health, National Heart Lung and Blood Institute Grant Number UM1- HL112856 and National Center for Advancing Translational Sciences, Grant Numbers UL1TR001422 and UL1TR002003.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Study Objectives: There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. Methods: By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. Results: At baseline, overall apnea–hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m2, and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by ?3.8 ± 0.8 points from baseline (p < .0001) and by ?2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. Conclusions: These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.

AB - Study Objectives: There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. Methods: By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. Results: At baseline, overall apnea–hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m2, and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by ?3.8 ± 0.8 points from baseline (p < .0001) and by ?2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. Conclusions: These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.

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KW - Clinical trial

KW - Obstructive sleep apnea

KW - Pharmacotherapy

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Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea

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