CAN BREATHE in COPD Trial

Study Overview
=================
Brief Summary
-----------------
A growing body of physiological evidence now exists to support a potential role for inhaled cannabis in the medical management of adults with chronic obstructive pulmonary disease (COPD), particularly as it may related to improving pulmonary function, alleviating the symptom of breathlessness and improving exercise endurance. The purpose of this randomized double-blind crossover trials is to evaluate the efficacy and physiological mechanism(s) of action of inhaled vaporized cannabis targeted to relief of physical activity-related breathlessness and exercise endurance in symptomatic patients with severe-to-very severe COPD.

Official Title
-----------------
Effect of Inhaled Vaporized Cannabis on Pulmonary Function, Breathlessness and Exercise Tolerance in Symptomatic Patients With Advanced Chronic Obstructive Pulmonary Disease (COPD)

Conditions
-----------------
Chronic Obstructive Pulmonary Disease (COPD), Breathlessness, Exercise Intolerance

Intervention / Treatment
-----------------
* Drug: Cannabis
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: GOLD stage III or IV COPD (i.e., post-β2-agonist FEV1 of 50% predicted or less) Self-reported cigarette smoking history ≥10 pack yrs Currently taking long-acting beta-2 agonists and long-acting antimuscarinic agents (LABA/LAMAs) with or without an inhaled corticosteroid Willing to abstain from cannabis smoking for ≥15 days prior to study participation (if applicable) Willing to abstain from non-study related cannabis smoking throughout the study period (if applicable) No change in medication dosage or frequency of administration, with no exacerbations or hospitalizations in the preceding 4 weeks Exclusion Criteria: Presence of active and/or uncontrolled cardiopulmonary and/or musculoskeletal disease other than COPD that could contribute to breathlessness and exercise intolerance Hepatic or renal impairment Psychiatric history (other than depression and/or anxiety) History of epilepsy or convulsions; Lung cancer History of sensitivity to cannabis Use of levodopa, sildenafil and/or fentanyl Use of ketoconazole Use of regular high dose opioids (i.e., 30 mg of oral morphine equivalents/day) Known or suspected history of addiction/substance abuse based on CAGE-AID and SISAP scores (*note, patients may be recruited if they have a history of smoking cannabis) Positive urine toxicology for cannabinoids on screening Positive pregnancy urine test Subject cannot arrange to be accompanied home by a family member and/or friend during each treatment visit.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>35 mg of tetrahydrocannabinol/cannabidiol (LT1.0/LT1.0 %) in vaporized form. Placebo will be vaporized using the Volcano Medic vaporizer. Total volume of vapour administered to each patient will be 5.5 L. | Drug: Placebo<br>* Patients will be administered placebo (cannabis stripped of cannabinoids) in vaporized form.<br>|
| Active Comparator: Cannabis<br>35 mg of cannabis (tetrahydrocannabinol/cannabidiol; 18.0/LT1.0 %) in vaporized form. THC/CBD will be vaporized using the Volcano Medic vaporizer. Total volume of vapour administered to each patient will be 5.5 L. | Drug: Cannabis<br>* Patients will be administered cannabis (THC/CBD) in vaporized form.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in intensity ratings of perceived breathlessness at isotime during cycle exercise testing. | Patients will be required to rate the intensity of their breathlessness using Borg's modified 0-10 category ratio scale every 2-minutes during cycle exercise testing. | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Changes in cycle exercise endurance time. | Exercise endurance time will be defined as the duration of loaded pedaling during the constant-load cycle exercise testing performed at 75% of peak incremental power output. | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Spirometry | Spirometry will be performed before and 5-min after treatment administration | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Changes in Impulse oscillometry | Impulse oscillometry will be performed before and 10-min after treatment administration | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Changes in Physiological responses during exercise. | Gas exchange, cardiovascular and breathing pattern variables will be collected breath-by-breath and averaged in 30-sec epochs during incremental and constant-load cycle exercise tests. | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Plasma cannabinoid levels. | Venous blood samples for the determination of circulating levels of cannabinoids will be collected before and 2-, 30-, 75-, and 180-min after vaporization | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Psychoactive effects. | Psychoactive effects of cannabis will be evaluated during each treatment visit using 100-mm visual analogue scale (VAS). Psychoactive effects will be evaluated before and 45-min after treatment administration. | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Mood effects. | Mood effects of cannabis will be evaluated during each treatment visit using 100-mm visual analogue scale (VAS). Mood effects will be evaluated before and 45-min after treatment administration. | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 
| Cognitive effects. | Cognitive effects will be measured during each treatment visit using the mini-mental state exam. The mini-mental state exam will be administered before and 45-min after treatment administration | Participants will be followed until all study visits are complete, an expected average of 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cannabis, Marijuana