Safety and Efficacy Study of Dronabinol to Treat Obstructive Sleep Apnea (PACE)

• ClinicalTrials.gov Identifier: NCT01755091
• Recruitment Status: Completed
• First Posted: December 21, 2012
• Results First Posted: December 22, 2017
• Last Update Posted: December 22, 2017
• Sponsor: University of Illinois at Chicago
• Collaborators: Northwestern University; University of Chicago; Hektoen Institute for Medical Research
• Information provided by (Responsible Party): David W. Carley, University of Illinois at Chicago

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Sleep Apnea, Obstructive	Drug: Dronabinol; Drug: Placebo (for Dronabinol)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cannabimimetic Treatment of Obstructive Sleep Apnea: A Proof of Concept Trial
• Study Start Date: February 2013
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: December 31, 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Sugar Pill; Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in	Drug: Placebo (for Dronabinol)
Experimental: 2.5 mg/day; Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in	Drug: Dronabinol
Experimental: 10 mg/day; Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation	Drug: Dronabinol

Outcome Measures

Primary Outcome Measures :

1. Change in Apnea/Hypopnea Index (AHI) [ Time Frame: Baseline and Week 6 ]
   Change in AHI derived as: AHI (end of treatment) minus AHI (pre-treatment)
2. Change in Epworth Sleepiness Scale (ESS) [ Time Frame: Baseline and Week 6 ]
   Change in ESS derived as: ESS (end of treatment) minus ESS (pre-treatment). The ESS scale has a range of 0 to 24, with 0 representing the least degree of sleepiness and 24 the greatest degree of sleepiness. There are no subscales.
3. Change in Sleep Latency: Maintenance of Wakefulness Test (MWT) [ Time Frame: Baseline and Week 6 ]
   Change in MWT derived as: MWT (end of treatment) minus MWT (pre-treatment). The Maintenance of Wakefulness Test measures a person's ability to stay awake in a quiet, dark and nonstimulating room for a period of time.

Secondary Outcome Measures :

1. Tolerability by Treatment Satisfaction Questionnaire for Medications (TSQM) Overall Score. [ Time Frame: Week 6 ]
   The TSQM measures a person's satisfaction with treatment based on a 7-point scale ranging from "Extremely Dissatisfied" to "Extremely Satisfied" in response to the question, "Taking all things into account, how satisfied or dissatisfied are you with this medication?".
2. Adverse Events (AEs) [ Time Frame: Up to 8 weeks ]
   AEs will be evaluated and tracked throughout subject participation (up to 8 weeks)
3. Change in Desaturation Time (DT) [ Time Frame: 6 weeks ]
   Change in DT (total minutes with arterial oxygen saturation below 85% during 8-hour polysomnography) derived as: DT (end of treatment) minus DT (pre-treatment)

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

Sponsors and Collaborators

University of Illinois at Chicago

Northwestern University

University of Chicago

Hektoen Institute for Medical Research

Investigators

• Principal Investigator: David W Carley, PhD; University of Illinois at Chicago

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). doi: 10.1093/sleep/zsx184.

• Responsible Party: David W. Carley, Professor, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT01755091
• Other Study ID Numbers: UM1HL112856 2011-06400; UM1HL112856 ( U.S. NIH Grant/Contract )
• First Posted: December 21, 2012
• Results First Posted: December 22, 2017
• Last Update Posted: December 22, 2017
• Last Verified: November 2017

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Dronabinol; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists