Reducing Breathlessness With Dronabinol in COPD Patients (BONG)

BONG: Reducing Severe Breathlessness With Dronabinol in the Severe and Very Severe Chronic Obstructive Pulmonary Disease Patient Group - A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

This clinical trial examines whether Dronabinol, which contains the synthetic psychoactive compound tetrahydrocannabinol (THC), can alleviate severe breathlessness in patients with severe and very severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Recruiting
• Conditions: Cannabis; COPD; Breathlessness
• Intervention / Treatment: Drug: Dronabinol 2.5mg Capsule; Drug: Placebo

Detailed Description

This study is a randomized, controlled, double-blind, crossover trial evaluating the effectiveness of the pharmaceutical drug Dronabinol in patients with severe and very severe COPD.

The researchers will compare the effects of Dronabinol with a placebo (an identical-looking substance that contains no active drug) to determine if Dronabinol reduces breathlessness in COPD patients.

After enrollment, study subjects will undergo four weeks of treatment with both Dronabinol and the placebo in a blinded and randomized sequence. There is a two-week washout period between treatments. During these treatment phases, subjects will complete questionnaires about their daily experiences of breathlessness and wear a watch that records various health parameters.

The study includes eight visits: the initial enrollment and follow-up checks every two weeks. At these visits, subjects undergo tests for lung function and walking distance, and complete health status questionnaires. Additionally, blood samples for THC levels and hair samples for cortisol analysis are collected.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Vejle Hospital
• Study Contact Backup: Name: Sofie K Wolsing, MSc, RN; Phone Number: +45 79409055; Email: swolsing@health.sdu.dk

Study Locations

• Denmark
  • Region Syddanmark
    • Vejle, Region Syddanmark, Denmark, 7100
      • Recruiting
      • Vejle Hospital - A part of Lillebaelt Hospital
      • Contact: Sofie K Wolsing; Phone Number: 0045; Email: swolsing@health.sdu.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Refractory dyspnea despite optimal treatment
• COPD (GOLD 3,4)
• Breathlessness corresponding to mMRC score ≥ 3
• Informed written consent
• Age ≥ 18 years
• Cognitive relevant, of legal age
• Understands and speaks Danish
• For fertile women defined by amenorrhea for less than 12 months: negative HCG before entry into the trial
• For fertile and sexually active subjects: use of safe contraception during medication intake and 4 weeks after: intrauterine device (IUD) or hormonal contraception (oral contraceptive pill, implant, transdermal patch, vaginal ring or depot injection).

Exclusion Criteria:

• Ongoing infection or exacerbation of COPD within the last month (30 days)
• Regular treatment with THC or CBD within 1 month (30 days)
• Life expectancy less than 3 months (90 days)
• Treatment with medicines that, according to the summary of product characteristics, are strong inhibitors or inducers of CYP3A4, CYP2C9 or CYP2C19
• History of or current evidence of significant medical or psychiatric disorder that is considered by the investigator to put the subject at greater risk of experiencing an adverse event
• Current or past substance abuse where the investigator finds it too risky for the subject to be included in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dronabinol 20 mg, then placebo; In this arm, the study subject will first receive dronabinol 2.5 mg capsules. For two weeks the subject will titrate dose with one capsule corresponding to 2.5 mg dronabinol every other day until 20 mg. Doses are divided into three times a day. After up titration the subject will receive 20 mg daily treatment over a period of 2 weeks. After a wash out period of 2 weeks, study subject will receive placebo capsules (matching dronabinol 2.5 mg capsules). For two weeks the subject will titrate with one capsule every other day until 20 mg. Doses are divided into three times a day. After up titration the subject will receive 8 daily placebo capsules over a period of 2 weeks.	Drug: Dronabinol 2.5mg Capsule; Dronabinol 2.5 mg pr capsule. Titration up till 20 mg daily dose.; Other Names: Delta9-tetrahydrocannabinol; Drug: Placebo; Dronabinol-matched placebo capsule containing no active substance.
Placebo Comparator: Placebo, then dronabinol 20 mg; In this arm, the study subject will first receive placebo capsules (matching dronabinol 2.5 mg capsules). For two weeks the subject will titrate with one capsule every other day until 20 mg. Doses are divided into three times a day. After up titration the subject will receive 8 daily placebo capsules over a period of 2 weeks. After a wash out period of 2 weeks, study subject will receive dronabinol 2.5 mg capsules. For two weeks the subject will titrate dose with one capsule corresponding to 2.5 mg dronabinol every other day until 20 mg. Doses are divided into three times a day. After up titration the subject will receive 20 mg daily treatment over a period of 2 weeks.	Drug: Dronabinol 2.5mg Capsule; Dronabinol 2.5 mg pr capsule. Titration up till 20 mg daily dose.; Other Names: Delta9-tetrahydrocannabinol; Drug: Placebo; Dronabinol-matched placebo capsule containing no active substance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Numeric Rating Scale score of discomfort of daily breathlessness between active treatment and placebo	Numeric rating scale score range 0-10. Higher score reflects higher discomfort of breathlessness	Assessed daily in the baseline period and through both treatment periods. Up to 70 days
Difference in Numeric Rating Scale score of breathlessness interference of daily activities between active treatment and placebo	Numeric rating scale score range 0-10. Higher score reflects more breathlessness interference on daily activities	Assessed daily in the baseline period and through both treatment periods. Up to 70 days
Correlation between breathlessness rated on a daily numeric rating scale in relation to amount of THC blood level of the active treatment period	Numeric rating scale score range 0-10. Higher score reflects higher discomfort of breathlessness	Assessed daily in the baseline period and through both treatment periods. Up to 70 days
Correlation between breathlessness interference of daily activities rated on a numeric rating scale in relation to amount of THC blood level of the active treatment period	Numeric rating scale score range 0-10. Higher score reflects more breathlessness interference on daily activities	Assessed daily in the baseline period and through both treatment periods. Up to 70 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Multidimensional Dyspnea Profile questionnaire score between active treatment and placebo period	Assesses different dimensions of COPD.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in COPD Assessment Test questionnaire score between active treatment and placebo period	Assesses the severity of physical COPD symptoms.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in Chronic Respiratory Disease Questionnaire score between active treatment and placebo period	A HRQL tool which incorporates patient perceptions of both physical and emotional health.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in Hospital Anxiety and Depression Scale questionnaire score between active treatment and placebo period	Assess anxiety and depression symptoms in medical patients.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in Medical Research Council Dyspnea Scale questionnaire score between active treatment and placebo period	A simple and valid method of categorizing patients with COPD in terms of their disability that could be used to complement FEV1 in the classification of COPD severity.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in Epworth Sleepiness Scale questionnaire score between active treatment and placebo period	Assesses person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in the spirometry parameter forced expiratory volume in 1. second (FEV1) between active treatment and placebo period	The FEV1 indicates the lung tissue's ability to release air during the first second of exhalation.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in the spirometry parameter forced vital capacity (FVC) between active treatment and placebo period	The FVC indicates the lung tissue's ability to release air during the entire exhalation.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in the spirometry parameter FEV1/FVC (ratio), between active treatment and placebo period	Can indicate an obstructive pattern in the exhalation which are used in the diagnosis of COPD.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in six-minute walk test(6MWT) between active treatment and placebo period	6 minutes walking test measures breathlessness and performance ability.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference Borg dyspnea score conducted in relation to 6MWT between active treatment and placebo period	A numeric scale from 0 (no breathlessness) to 10 (extremely strong breathlessness) but not limited to 10 if subjects feel breathlessness above 10	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in cortisol level in the hair samples between active treatment and placebo period	Measurement of stress through cortisol levels in the hair.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in clinical parameters between active treatment and placebo period using a yet unspecified continuous monitoring device.	For several days in each treatment period we continuously measure blood oxygen saturation, electrodermal activity, pulse rate, sleep recording, temperature, respiratory rate, and activity counter.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)
Difference in stand-to-sit-test between active treatment and placebo	A measurement for physical capability until breathlessness.	Baseline (T1; day 1) and after each treatment period (T4; day 28, T7; day 70)

Collaborators and Investigators

• Sponsor: Vejle Hospital
• Collaborators: University of Aarhus; University of Southern Denmark; Region of Southern Denmark; Odense Patient Data Explorative Network
• Investigators: Principal Investigator: Ole Hilberg, Prof., MD, Medical Department, Vejle Hospital

Publications and helpful links

General Publications

• Wolsing SK, Hilberg O, Lokke A, Farver-Vestergaard I, Andersen CU, Hansen KK. Reducing severe breathlessness with dronabinol in the group of patients with severe and very severe chronic obstructive pulmonary disease (BONG): a randomised, double-blinded, placebo-controlled, crossover study in an outpatient clinic in Denmark - a study protocol. BMJ Open. 2026 Feb 16;16(2):e104957. doi: 10.1136/bmjopen-2025-104957.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: June 18, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: COPD; Cannabis; Breathlessness; Randomized, Controlled, Double-blind, Crossover trial; Cannabis-based medicine
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Substance-Related Disorders; Chemically-Induced Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Marijuana Abuse; Dyspnea; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol
• Other Study ID Numbers: 2024-513593-22-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is the plan to share SAP when this is finalized. It is undecided whether CSR and analytic code will be shared on a platform or available on reasonable request.

Drug and device information, study documents

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