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

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT01755091
• Collaborator: Northwestern University (Other), University of Chicago (Other), Hektoen Institute for Medical Research (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 75
• Locations: 2
• Arms: 3
• Duration (Months): 46.9
• Patients Per Site: 37.5
• Patients Per Site Per Month: 0.8

Study Details

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
• 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: Feb 1, 2013
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Dec 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) [Baseline and Week 6]

   Change in AHI derived as: AHI (end of treatment) minus AHI (pre-treatment)

2. Change in Epworth Sleepiness Scale (ESS) [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) [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. [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) [Up to 8 weeks]

   AEs will be evaluated and tracked throughout subject participation (up to 8 weeks)

3. Change in Desaturation Time (DT) [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	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
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David W. Carley, Professor, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT01755091
• Other Study ID Numbers: 2012-0095; UM1HL112856
• First Posted: Dec 21, 2012
• Last Update Posted: Jul 29, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Dronabinol

Study Results

Participant Flow

Recruitment Details	Participants were recruited from physician referrals at two academic medical centers as well as from the community based upon print and radio advertising between January 2013 and May 2016. The first participant was enrolled in February 2013 and the last participant was enrolled in April 2016.

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Period Title: Overall Study
STARTED	26	22	27
COMPLETED	17	19	20
NOT COMPLETED	9	3	7

Baseline Characteristics

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day	Total
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol	Total of all reporting groups
Overall Participants	26	22	27	75
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	26 100%	22 100%	27 100%	75 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 30.8%	6 27.3%	9 33.3%	23 30.7%
Male	18 69.2%	16 72.7%	18 66.7%	52 69.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 15.4%	5 22.7%	1 3.7%	10 13.3%
Not Hispanic or Latino	22 84.6%	17 77.3%	25 92.6%	64 85.3%
Unknown or Not Reported	0 0%	0 0%	1 3.7%	1 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 3.8%	0 0%	2 7.4%	3 4%
Native Hawaiian or Other Pacific Islander	0 0%	1 4.5%	0 0%	1 1.3%
Black or African American	15 57.7%	5 22.7%	13 48.1%	33 44%
White	9 34.6%	16 72.7%	12 44.4%	37 49.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.8%	0 0%	0 0%	1 1.3%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.39 (6.33)	33.19 (5.09)	33.45 (4.85)	33.35 (6.33)
Apnea/Hypopnea Index (events/hour) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [events/hour]	23.72 (9.47)	27.54 (12.57)	26.04 (11.92)	25.67 (11.29)
Minimum Arterial Oxygen Saturation (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	79.58 (9.62)	79.82 (6.83)	79.96 (6.93)	79.79 (7.84)
Sleep Efficiency (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	75.51 (12.50)	80.52 (11.11)	82.74 (12.22)	79.58 (12.25)

Outcome Measures

1. Primary Outcome

Title	Change in Apnea/Hypopnea Index (AHI)
Description	Change in AHI derived as: AHI (end of treatment) minus AHI (pre-treatment)
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Analysis performed including all participants who completed the full 6-weeks of treatment.

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	17	19	20
Mean (Standard Deviation) [events/hour]	7.99 (13.16)	-1.71 (11.74)	-5.21 (9.52)

2. Primary Outcome

Title	Change in Epworth Sleepiness Scale (ESS)
Description	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.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Data are missing for 2 participants randomized to receive Placebo treatment; due to technical error in not completing this instrument.

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	15	19	20
Mean (Standard Deviation) [units on a scale]	-1.47 (3.29)	-.26 (2.94)	-4.00 (5.13)

3. Primary Outcome

Title	Change in Sleep Latency: Maintenance of Wakefulness Test (MWT)
Description	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.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	17	19	20
Mean (Standard Deviation) [minutes]	-2.50 (13.09)	-3.70 (9.73)	1.40 (11.71)

4. Secondary Outcome

Title	Tolerability by Treatment Satisfaction Questionnaire for Medications (TSQM) Overall Score.
Description	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?".
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Data are missing for one participant randomized to receive Placebo treatment due to technical error in not collecting the instrument.

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	16	19	20
Extremely Dissatisfied	3 11.5%	2 9.1%	1 3.7%
Very Dissatisfied	1 3.8%	2 9.1%	0 0%
Dissatisfied	0 0%	3 13.6%	0 0%
Somewhat Satisfied	5 19.2%	6 27.3%	4 14.8%
Satisfied	1 3.8%	4 18.2%	4 14.8%
Very Satisfied	5 19.2%	1 4.5%	5 18.5%
Extremely Satisfied	1 3.8%	1 4.5%	6 22.2%

5. Secondary Outcome

Title	Adverse Events (AEs)
Description	AEs will be evaluated and tracked throughout subject participation (up to 8 weeks)
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	26	22	27
Mean (Standard Deviation) [Number of adverse events per participant]	3.4 (2.9)	2.8 (3.6)	5.8 (4.7)

6. Secondary Outcome

Title	Change in Desaturation Time (DT)
Description	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)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	2.5 mg/Day	10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)	Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol	Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
Measure Participants	17	19	20
Mean (Standard Deviation) [minutes]	1.21 (3.46)	-0.19 (2.78)	-0.17 (6.68)

Adverse Events

Arm/Group Title	Sugar Pill		2.5 mg/Day		10 mg/Day
Arm/Group Description	Placebo, once per day (QD) by mouth, 60 minutes before bedtime for 6 weeks after 1-week run-in Placebo (for Dronabinol)		Dronabinol, 2.5 mg QD by mouth, 60 minutes before bedtime for 6 weeks after 1-week placebo run-in Dronabinol		Dronabinol, 10 mg QD by mouth, 60 minutes before bedtime for 4 weeks after 1-week placebo run-in and 2-week dose escalation Dronabinol
All Cause Mortality
	Sugar Pill		2.5 mg/Day		10 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugar Pill		2.5 mg/Day		10 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)		1/22 (4.5%)		0/27 (0%)
Gastrointestinal disorders
Diarrhea	0/26 (0%)	0	1/22 (4.5%)	1	0/27 (0%)	0
Injury, poisoning and procedural complications
Cycling injury	1/26 (3.8%)	1	0/22 (0%)	0	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Sugar Pill		2.5 mg/Day		10 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/26 (34.6%)		13/22 (59.1%)		26/27 (96.3%)
Gastrointestinal disorders
Diarrhea	1/26 (3.8%)	1	3/22 (13.6%)	3	4/27 (14.8%)	4
Nausea	1/26 (3.8%)	1	5/22 (22.7%)	5	9/27 (33.3%)	9
Dry mouth	0/26 (0%)	0	0/22 (0%)	0	3/27 (11.1%)	3
Musculoskeletal and connective tissue disorders
Muscle aches	1/26 (3.8%)	1	2/22 (9.1%)	2	1/27 (3.7%)	1
Nervous system disorders
Sleepy	0/26 (0%)	0	0/22 (0%)	0	17/27 (63%)	17
Headache	4/26 (15.4%)	4	3/22 (13.6%)	3	13/27 (48.1%)	13
Dizziness	3/26 (11.5%)	3	1/22 (4.5%)	1	7/27 (25.9%)	7
Euphoria	0/26 (0%)	0	1/22 (4.5%)	1	2/27 (7.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.