Dronabinol for Sleep Apnea

(DROSA Trial)

Overseen By Karen M Lenehan

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Sedative-hypnotics, Antidepressants, Antipsychotics

Disqualifiers: Obesity, Alcohol use, Sleep disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Dronabinol for individuals with obstructive sleep apnea (OSA), a condition where breathing repeatedly stops and starts during sleep. The goal is to determine if taking Dronabinol for two weeks can improve sleep by reducing OSA severity. Participants will undergo sleep studies before and after taking the medication to measure changes. The trial seeks adults with moderate to severe OSA who are not regularly using other treatments like CPAP machines or oral devices. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot use sedative-hypnotic medications within 30 days of enrollment. Also, you should not start new antidepressant or antipsychotic medications within 3 months before the trial.

Is there any evidence suggesting that Dronabinol is likely to be safe for humans?

Research has shown that Dronabinol, a medicine derived from cannabis, has been tested in individuals with obstructive sleep apnea (OSA). Some studies found it can help reduce symptoms. However, 70% to 80% of participants reported side effects affecting the nervous system and stomach, such as dizziness or nausea. While Dronabinol might alleviate OSA symptoms, it can also cause uncomfortable side effects for many. Prospective trial participants should consider these potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea?

Unlike the standard treatments for sleep apnea, which often include CPAP machines or oral appliances, dronabinol offers a unique approach by utilizing a cannabinoid-based compound. Researchers are excited because dronabinol works by targeting the body's endocannabinoid system, which may help regulate sleep and breathing patterns in a novel way. This different mechanism of action could provide an alternative for patients who struggle with or prefer not to use conventional mechanical devices.

What evidence suggests that Dronabinol might be an effective treatment for sleep apnea?

Research has shown that dronabinol may help people with obstructive sleep apnea (OSA). One study found that dronabinol reduced the frequency of breathing interruptions during sleep and decreased daytime sleepiness. Another study demonstrated that participants reported greater satisfaction with their treatment when taking dronabinol compared to a placebo. While some evidence suggests that cannabinoids like dronabinol might help keep airways open, results have varied when taken orally. Overall, these findings suggest that dronabinol could be effective in treating OSA. Participants in this trial will receive open-label dronabinol treatment for two weeks to further evaluate its effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Bharati Prasad, MD

Principal Investigator

Jesse Brown VA Medical Center, Chicago, IL

Are You a Good Fit for This Trial?

This trial is for individuals with obstructive sleep apnea (OSA). Specific eligibility criteria are not provided, but typically participants would need a confirmed diagnosis of OSA and be in stable health to participate.

Inclusion Criteria

AHI 15-50 per hour on pre-treatment polysomnography

Exclusion Criteria

Active enrollment in a weight loss program

I have had surgery for sleep apnea, not including adenotonsillectomy.

My weight has been stable for 6 months after bariatric surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label Dronabinol treatment for two weeks

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol

Trial Overview The trial is testing the effectiveness of Dronabinol, an oral medication, in treating OSA. It's an open-label study where all participants will receive the drug for two weeks with sleep studies before and after treatment to assess changes.

How Is the Trial Designed?

Group I: Single group Experimental Treatment 1 Intervention

Open label Dronabinol treatment for two weeks.

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

The FDA approved Syndros, an oral solution containing dronabinol (delta-9-THC), on July 1, 2016, indicating its recognized therapeutic potential.

Following FDA approval, the DEA classified Syndros as a Schedule II controlled substance, reflecting its potential for abuse but also its accepted medical use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments. [2017]

In a proof-of-concept study involving 17 adults with Obstructive Sleep Apnea (OSA), dronabinol (Δ(9)THC) was found to be safe and well-tolerated at doses ranging from 2.5 to 10 mg daily.

Dronabinol significantly reduced the Apnea Hypopnea Index (AHI) by an average of 14.1 events per hour after 21 days of treatment, indicating its potential efficacy in managing OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof of concept trial of dronabinol in obstructive sleep apnea. Prasad, B., Radulovacki, MG., Carley, DW.[2021]

In a Phase II trial involving 73 adults with moderate to severe obstructive sleep apnea (OSA), dronabinol significantly reduced the apnea-hypopnea index (AHI) by up to 12.9 events/hour compared to placebo, indicating its potential efficacy as a treatment.

Participants taking 10 mg of dronabinol reported greater satisfaction with their treatment and experienced a significant reduction in daytime sleepiness, as measured by the Epworth Sleepiness Scale, suggesting that dronabinol may improve both sleep quality and overall well-being in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea. Carley, DW., Prasad, B., Reid, KJ., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39498540/

Cannabinoids for obstructive sleep apnea: A systematic ... Eight of nine total studies reported statistically significant, positive OSA outcomes due to cannabinoid therapy including reductions in the ...

2. academic.oup.com academic.oup.com/sleep/article/48/4/zsae276/7908945

randomized dose finding study of combination dronabinol and ... Our data showed that IHL-42X reduced OSA severity by 35%–40%, regardless of dose.

3. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.7070

Medical Cannabis and the Treatment of Obstructive Sleep ... Dronabinol reduces AHI and daytime sleepiness in patients with moderate to severe obstructive sleep apnea syndrome [abstract #0558]. Sleep; 2017 ...

4. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.4622

Cannabinoids for obstructive sleep apnea: A systematic review Data suggest cannabinoids may reduce airway resistance when administered via inhalation but results have been inconsistent when provided orally.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5806568/

Effects of Dronabinol in Obstructive Sleep Apnea - PMC In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01755091

NCT01755091 | Safety and Efficacy Study of Dronabinol to ... This is a proof of concept study to determine the safety and efficacy of dronabinol for the treatment of obstructive sleep apnea syndrome (OSA).