DRonabinol Treatment of OSA (DROSA)

Targeted Treatment of Obstructive Sleep Apnea With Dronabinol: Proof of Concept and Phase II Clinical Trial

This is an open-label trial that tests the effectiveness of Dronabinol in treating obstructive sleep apnea (OSA). All participants will take oral Dronabinol for two weeks. Sleep studies will be conducted before and after treatment to measure OSA severity.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Dronabinol

Detailed Description

Obstructive sleep apnea (OSA), is a serious respiratory disorder that involves repetitive cessation of breathing during sleep. It is estimated that 15-20 million people in the United States suffer from OSAS, which has been linked to increased risk for hypertension, heart failure, depression, and diabetes. The current standard of care for OSA, positive airway pressure (PAP), involves a mechanical device with low patient tolerance and adherence. Upper airway surgical approaches are also an option but are invasive and often unsuccessful. Effective drug treatments for OSA remain to be identified.

This study will enroll up to 120 Veterans so that 45 Veterans may complete the two-week open-label Dronabinol treatment trials. The results of the study will be used to develop a prediction model for OSA severity reduction after 2-week Dronabinol treatment vs. pretreatment AHI. Participants clinical (age, sex, body mass index, comorbidity) and pretreatment polysomnographic characteristics (sleep architecture, respiratory disturbance, and endotypes; loop-gain, arousal threshold, upper airway collapsibility and compensation) will be used to develop a prediction model for improvement of OSA with Dronabinol treatment. This prediction model will be used for a randomized clinical trial after the completion of this trial.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Karen M Lenehan; Phone Number: (312) 569-6343; Email: Karen.Lenehan@va.gov
• Study Contact Backup: Name: Bharati Prasad, MD; Phone Number: (312) 996-8433; Email: bharati.prasad@va.gov

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Jesse Brown VA Medical Center, Chicago, IL
      • Contact: Howard S Gordon, MD BS; Phone Number: (312) 569-7331; Email: howard.gordon2@va.gov
      • Contact: Karen M Lenehan; Phone Number: 312-569-6343; Email: Karen.Lenehan@va.gov
      • Principal Investigator: Bharati Prasad, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults 18 to 65 years of age.
2. AHI 15-50 per hour on pre-treatment polysomnography.

Exclusion Criteria:

1. Positive Airway Pressure (PAP) treatment of OSA: use > 4 hours per day for 30% of days within 3 months of enrollment. PAP use will be determined from device download data.
2. Hypoglossal nerve stimulator (HNS) or oral appliance device treatment with use > 4 hours per day for 30% of days within 3 months of enrollment. HNS use will be determined by device download and oral appliance use by self-report.
3. History of upper airway surgery for OSA (except adenotonsillectomy).
4. Central or mixed apneas >25% of respiratory events on diagnostic polysomnography.
5. Arterial oxygen saturation < 75% for > 5% sleep time on pretreatment polysomnography.
6. Body mass index > 45 kg/m2.
7. If post-bariatric surgery, weight must be stable ±5% (per electronic medical records) for at least 6 months before the first dose of the study drug.
8. Active enrollment in a weight loss program.
9. Shiftwork within 3 months of enrollment.
10. High-risk occupation: commercial driver and pilot.
11. Motor vehicle accident or near-miss incident within 1 year of enrollment.
12. Current drug or habitual alcohol use or positive urine drug screen.

13. Comorbid medical and psychiatric disorders:

    1. Primary sleep disorders: e.g., narcolepsy, restless legs syndrome.
    2. Uncontrolled mood disorder or a diagnosis of schizophrenia.
    3. Initiation of new antidepressant or antipsychotic medication within 3 months.
    4. Identified as high-risk for suicide in electronic health records.
    5. Uncontrolled medical disorders (coronary heart disease, arrhythmia, congestive heart failure, chronic obstructive pulmonary disease, chronic hypoxemic or hypercapnic respiratory failure, stroke within 6 months of enrollment, chronic liver or kidney disease, autoimmune disorders).
14. Use of sedative-hypnotic medications within 30 days of enrollment.
15. Complete blood count or liver function test values more than 1.5 times the upper limit of normal.
16. Pregnancy.
17. Allergy to cannabinoids or sesame oil.
18. Average weekly alcohol consumption of more than 10 servings.
19. Participation in other investigational protocols within 30 days of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single group; Open label Dronabinol treatment for two weeks.	Drug: Dronabinol; Open label Dronabinol treatment for two weeks.; Other Names: Marinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea hypopnea index (AHI)	The change in AHI after two weeks of Dronabinol treatment will be determined from before and after treatment polysomnograms.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T<90	The change in time below 90% oxygen saturation (T<90) after two weeks of Dronabinol treatment will be determined from before and after treatment polysomnograms.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychomotor Vigilance Test (PVT)	The change in Lapses on Psychomotor Vigilance Test (PVT) after two weeks of Dronabinol treatment will be determined from before and after treatment PVT using a 10 minute protocol.	2 weeks
24-hour mean arterial blood pressure (BP)	The change in 24- hour mean arterial blood pressure after two weeks of Dronabinol treatment will be determined from before and after treatment 24-hiur ambulatory BP recording.	2 weeks
Sleep Efficiency	The change in sleep efficiency after two weeks of Dronabinol treatment will be determined from before and after treatment polysomnograms.	2 weeks
REM sleep	The change in REM sleep after two weeks of Dronabinol treatment will be determined from before and after treatment polysomnograms.	2 weeks
Slow wave sleep	The change in slow wave sleep after two weeks of Dronabinol treatment will be determined from before and after treatment polysomnograms.	2 weeks
Treatment Satisfaction Questionnaire for Medication (TSQM)	Patient reported treatment satisfaction. TSQM scores have a range of 0 to 100, with higher scores indicating higher satisfaction.	2 weeks
Epworth Sleepiness Scale (ESS)	The change in Epworth Sleepiness Scale (ESS) will be measured after two weeks of Dronabinol treatment. ESS scores have a range of 0 to 24, with higher scores indicating greater sleepiness.	2 weeks
Functional Outcomes of Sleep Questionnaire (FOSQ)	The change in Functional Outcomes of Sleep Questionnaire (FOSQ) will be measured after two weeks of Dronabinol treatment. FOSQ score ranges from 5-20, with higher scores indicating better functional status.	2 weeks
Pittsburgh Sleep Quality Index (PSQI)	The change in Pittsburgh Sleep Quality Index (PSQI) will be measured after two weeks of Dronabinol treatment. The PSQI score ranges from 0 to 21. Higher scores indicate poorer sleep quality.	2 weeks
Insomnia Severity Index (ISI)	The change in Insomnia Severity Index (ISI) will be measured after two weeks of Dronabinol treatment. ISI ranges from 0 to 28, with higher scores indicating greater sleep disturbance.	2 weeks
Post-Traumatic Stress Disorder; PTSD checklist (PCL-5)	The change in Post-Traumatic Stress Disorder; PTSD checklist (PCL-5) will be measured after two weeks of Dronabinol treatment. PCL-5 scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.	2 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of Illinois at Chicago
• Investigators: Principal Investigator: Bharati Prasad, MD, Jesse Brown VA Medical Center, Chicago, IL

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: OSA; Drug treatment; sleep apnea; pharmacological treatment
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol
• Other Study ID Numbers: PULM-011-23F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes