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Clinical Trial
. 2018 Jan 1;41(1):zsx184.
doi: 10.1093/sleep/zsx184.

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea

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Free PMC article
Clinical Trial

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea

David W Carley et al. Sleep. .
Free PMC article

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.

Trial registration: ClinicalTrials.gov NCT01755091.

Keywords: cannabinoid; clinical trial; obstructive sleep apnea; pharmacotherapy.

Figures

Figure 1.
Figure 1.
Workflow diagram illustrating the disposition of 417 enrolled in the protocol.
Figure 2.
Figure 2.
Efficacy of dronabinol after 6 weeks of treatment. Bars depict mean ± SE for each treatment group. (A) Change from baseline in AHI. *p = .02 versus Placebo. **p = .003 versus Placebo. Mean values for 2.5 and 10 mg/day did not differ significantly (p = .60). ++p = .01 versus no change from baseline AHI. (B) Change from baseline in ESS total score. *p = .05 versus Placebo; p = .002 versus 2.5 mg/day and p < .0001 versus no change from baseline. ESS score for Placebo and 2.5 mg/day groups did not differ from baseline values. (C) Change from baseline in MWT mean sleep latency. ∆MWT sleep latency was equivalent among all treatment groups and the mean change was not different from zero in any treatment group.
Figure 3
Figure 3
Treatment-related changes in AHI individual “responders.” Each panel depicts the AHI measured at baseline and at the end of treatment for a single responder (square symbols). In addition, AHI stratified according the NREM sleep (diamond symbols) and REM sleep (circle symbols) are depicted for each of these participants.

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