Clinical trial NCT01755091: Safety and Efficacy Study of Dronabinol to Treat Obstructive Sleep Apnea
Official title: Cannabimimetic Treatment of Obstructive Sleep Apnea: A Proof of Concept Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sleep Apnea, Obstructive
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Northwestern University
name: University of Chicago
name: Hektoen Institute for Medical Research
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-12-21
Enrollment: 75
Sex: ALL
Minimum age (years): 21
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a proof of concept study to determine the safety and efficacy of dronabinol for the treatment of obstructive sleep apnea syndrome (OSA).


Eligibility criteria: Inclusion Criteria:

* Adult 21 to 64 years of age;
* 15≤AHI ≤ 50 on screening polysomnogram (PSG)
* ESS score ≥ 7
* Able to understand and complete informed consent and all study assessments and forms, presented in an English-speaking format;
* Women of child-bearing potential (WCBP) must have a negative urine pregnancy test. In addition sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable or implantable hormonal contraceptive; tubal ligation; intra-uterine devices; barrier contraceptive with spermicide; or vasectomized partner).

Exclusion Criteria:

* Arterial oxygen saturation \< 75% for \> 5% of sleep period time on screening PSG;
* Occupation or life situation that may impart risk by study participation (e.g. commercial driver, pilot, police officer, fireman);
* Motor vehicle accident or "near-miss" related to sleepiness (self-report) within 2 years of the first dose of study drug (Day 8);
* Body mass index \> 45 kg/m2
* Severe obstructive sleep apnea syndrome (OSAS) that, based on the clinical judgment of the Investigator, precludes delaying positive airway pressure treatment;
* History of shift work or rotating shifts within the month prior to the first dose of study drug (Day 8);
* Prior upper airway surgery for snoring or OSAS as an adult (≥ 18 years of age);
* Prior non-invasive treatment for OSAS within 6 months prior to the first dose of study drug (Day 8);
* Major surgery within 6 months prior to the first dose of study drug (Day 8);
* Bariatric surgery within 2 years prior to the first dose of study drug (Day 8). If post-bariatric surgery, weight must be stable ±5% (self-report) for at least 6 months prior to first dose of study drug (Day 8).
* Any form of medically managed weight loss program within 6 months prior to the first dose of study drug (Day 8);
* Significant defect in nasal patency due to anatomical abnormalities or uncontrolled or recurrent episodes of rhinitis;
* Any clinically significant unstable or progressive medical condition;
* Any primary sleep disorder other than OSAS as determined by history, physical examination, or Visit 2 PSG (after 7-day screening run-in period);
* Clinically significant or uncontrolled: chronic obstructive pulmonary disease (COPD), cardiovascular disease, gastrointestinal, respiratory, pancreatic, hepatic, renal, hematologic, endocrine \[including insulin-dependent diabetes mellitus (IDDM)\], neurological, urogenital, connective tissue, dermatological, thyroid, or other medical disorder;
* Any clinically significant psychiatric disorder;
* History of seizure disorder;
* Treatment with any prescription antidepressant medication within 1 month prior to the first dose of study drug (Day 8);
* Treatment with sedatives, hypnotics or other psychoactive drugs within 30 days prior to the first dose of study drug (Day 8);
* Any complete blood count (CBC) or liver function test (LFT) laboratory value outside the normal range which, in the clinical judgment of the Investigator renders a subject inappropriate for randomization to treatment;
* Pregnancy \[as demonstrated by positive urine human chorionic gonadotropin (hCG) test\] or lactation;
* Allergic to cannabinoids or sesame oil;
* History of substance abuse (including alcohol abuse or dependence) or laboratory evidence of drug abuse on the Visit 1 drug-screening panel;
* Use of dietary supplements which in the judgment of the Investigator may impact sleep or breathing behaviors;
* Average daily caffeine consumption \> 500 mg/day (\~5 cups of coffee);
* Average weekly alcohol consumption \> 10 units;
* Unwillingness to abstain from caffeine and alcohol on all days when overnight or daytime testing will be performed;
* Participation in any other investigational protocol within the 30 days prior to the first dose of study drug (Day 8);
* Any condition which, in the opinion of the Investigator, places the patient at unacceptable risk if he or she were to participate in the study.

Primary outcomes:
measure: Change in Apnea/Hypopnea Index (AHI)
timeFrame: Baseline and Week 6
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: Baseline and Week 6
measure: Change in Sleep Latency: Maintenance of Wakefulness Test (MWT)
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Tolerability by Treatment Satisfaction Questionnaire for Medications (TSQM) Overall Score.
timeFrame: Week 6
measure: Adverse Events (AEs)
timeFrame: Up to 8 weeks
measure: Change in Desaturation Time (DT)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: David W Carley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carley DW, Prasad B, Reid KJ, Malkani R, Attarian H, Abbott SM, Vern B, Xie H, Yuan C, Zee PC. Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea. Sleep. 2018 Jan 1;41(1):zsx184. doi: 10.1093/sleep/zsx184.