A randomized dose finding study of combination dronabinol and acetazolamide for the treatment of obstructive sleep apnea.
Walsh et al.·SleepImpact 0.6
Clear benefitGRADEModerate5 citations
Samplen = 11 Pat.
Duration1 week per treatment arm
ControlPlacebo
EndpointAHI
Blindingdoppelblind
DesignRCT (crossover, dose-finding)
Cannabinoidthc
Routeoral
”Key finding
IHL-42X showed significant reduction of AHI compared to placebo at all three doses (low: -19,7, medium: -17,5, high: -16,4 vs. placebo: -2,8 events/hour), without serious adverse effects.
Summary
n=11, randomised double-blind placebo-controlled crossover study (dose titration); dronabinol + acetazolamide (IHL-42X) vs. placebo in obstructive sleep apnea (AHI ≥15/h). AHI reduction versus placebo: low dose −19,7±27,1, medium −17,5±23,3, high −16,4±23,8 events/h (all p<.05 vs. placebo −2,8±21,0). ODI3% reduction medium dose −15,4±19,0 vs. placebo (p<.05). ESS and mood unchanged; no serious adverse effects.
P
PopulationAdults with obstructive sleep apnea (AHI ≥15 events/hour), n=11
I
InterventionCombination preparation IHL-42X (dronabinol + acetazolamide) in three dose levels (low, medium, high), nightly oral, 1 week per arm
C
ControlPlacebo (double-blind, crossover)
O
OutcomeSignificant AHI reduction versus placebo at all three dose levels (low: −19,7; medium: −17,5; high: −16,4 vs. placebo: −2,8 events/hour; all p<0,05); ODI3% significant only at medium dose (p<0,05)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeClear benefit
Citations / year★★★★★
Authors
Walsh J, Rankin T, Mehra S, Naughton MT, Roebuck T, McDermott E, Pattichis A, Smith R, Walsh R, Bleackley M, Maddison K, O'Brien TJ
Current treatments for obstructive sleep apnea (OSA) are ineffective or not tolerated in a proportion of patients. Other therapeutic options are needed and pharmaceuticals may provide an alternative. This randomized, double-blind, placebo-controlled, crossover study examined the effect of a combination of acetazolamide and dronabinol (IHL-42X) at low, medium, and high doses on OSA severity. Participants with OSA (apnea-hypopnea index; AHI ≥15 events/hour) received 1 week of IHL-42X at each of three doses and placebo, each separated by a 1-week washout. The change from baseline in AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), and mood (profile of mood states) on the final night of each treatment arm relative to the change from baseline to placebo were the major endpoints. Adverse events (AEs) were monitored throughout. Ten of 11 participants completed the final night of at least one treatment arm. IHL-42X demonstrated a greater reduction in AHI from baseline compared with placebo (low, -19.7±27.1; medium, -17.5±23.3; high, -16.4±23.8 vs. placebo, -2.8±21.0 events/hour; all p<.05). The change from baseline in ODI3% was greater for the medium IHL-42X dose when compared with placebo (-15.4±19.0 vs. placebo, -2.8±21.0 events/hour; p<.05) but not the low or high doses (low, -15.2±24.8; high, -8.3±13.2 events/hour). IHL-42X did not change ESS or mood. No serious AEs occurred; however, 35 mild-moderate possibly, probably, or treatment-related AEs occurred during IHL-42X dosing and 5 occurred during placebo. One week of nightly IHL-42X at low, medium, and high doses was well tolerated, safe, and associated with significant reductions in OSA severity.