- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02324777
Cannabinoid Profile Investigation of Vapourized Cannabis in Patients With Osteoarthritis of the Knee (CAPRI)
A Randomized Double Blind Placebo Controlled, Proof-of-concept, Crossover Clinical Trial of Vapourized Cannabis in Adults With Painful Osteoarthritis of the Knee
Primary Objective:
- To determine the analgesic dose-response characteristics of vapourized cannabinoids with varying degrees of delta-9-tetrahydrocannabiol (THC)/ Cannabidiol (CBD) ratios.
Secondary Objectives:
- To compare functional changes and patient preferences of different cannabinoid (THC, CBD) profiles in patients with OA (Osteoarthritis);
- To describe the Pharmacokinetics (PK) of vapourized cannabis of differing cannabinoid profiles in patients with OA;
- To explore the short term safety of vapourized cannabis with different cannabinoid profiles.
- To describe the incidence and severity of psychoactive events.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A Phase IIa randomized double blind placebo controlled crossover trial (RCT) using six different herbal cannabis drug product formulations prepared by the Sponsor, Prairie Plant Systems Inc. An initial screening period (minimum one week) will be completed for pain assessment and determination of eligibility. After screening, eligible subjects will be randomly assigned to receive all 6 different formulations in a random order.
The study will be conducted using six periods of 7 days duration, with each period consisting of one day of exposure and 6 days of washout from study drug. The study will therefore take 6 weeks to be completed for each enrolled subject with an additional week for adverse event monitoring after the final study exposure. Total time in study may therefore be a maximum of nine weeks (including screening).
Adult subjects (age ≥50y) will be recruited with chronic (>3 months) moderate to severe pain (pain score ≥40/100 on visual analogue scale) due to primary osteoarthritis (OA) of the knee as defined by American College of Rheumatology (ACR) criteria. Target enrolment for this study is 36 (18 from each site).
The study will be conducted at the Alan Edwards Pain Management Unit of the McGill University Health Centre, in Montreal, Quebec, Canada and the Pain Management Unit at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, Canada. A dedicated ventilated room is available at these sites for cannabinoid inhalation studies as used in prior evaluation trials on medicinal cannabis.
All subjects meeting eligibility criteria after the screening period will be randomized to receive all 6 herbal cannabis drug product formulations in a randomly assigned order of treatment between Clinical Visit (CV) 2 and CV7.
A washout period of 6 days is proposed between the six different treatment periods. This will allow the pharmacological effects of each dose to be minimized prior to each subsequent dosing period to avoid confounding.
Throughout the study all subjects will remain on their stable (pharmacological and non-pharmacological) treatment regimen.
Throughout the study, subjects will be blinded to the treatment they are receiving. Once a subject has been randomized, the investigator and the subject, as well as all staff involved in the conduct or management of the study will be blinded to the treatment assignment. All dosing will be via the Volcano® Medic vapourizer (licensed for medical administration of cannabis in Canada March 2010; Licence No. 82405) and both the nurse and the patient will be familiarized with its instruction manual.
The study nurse will prepare the dose for the subject. After opening the vial of drug product formulation, its contents will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed to it (this balloon will be housed within an opaque bag that is required to ensure blinding because the placebo generates little in the way of visible vapour). Active components (THCA and CBDA decarboxylated to THC and CBD) will be vapourized out of the herbal material by a stream of hot air with an exact, predefined temperature (190 °C). The ensuing vapour will be captured in the balloon. After filling has been completed (35 seconds), a mouthpiece will be attached to the balloon for inhalation of the vapour by the study subject. The total contents of the balloon will be inhaled over five minutes by using a standardized inhalation technique. Immediately after the bag has been removed from the Volcano® Medic, inhalation will be according to the following regimen:
- Inhale for 4 seconds
- Hold breath for 6 seconds
- Exhale and breathe normally for 20 seconds
- Repeat this inhale-hold-breathe cycle (30 seconds) until the bag has been evacuated.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Angela D Perry, MSc
- Phone Number: 1283 306-975-1207
- Email: adp@prairieplant.com
Study Contact Backup
- Name: Larry A Hollbrook, PhD
- Phone Number: 1243 306-975-1207
- Email: lah@prairieplant.com
Study Locations
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada, B3H 1V7
- Recruiting
- Pain Management Unit, Queen Elizabeth II Health Sciences Centre
-
Contact:
- Melissa Todd
- Phone Number: (902) 473-7475
- Email: melissa.todd@nshealth.ca
-
Principal Investigator:
- Mary Lynch, MD
-
-
Quebec
-
Montreal, Quebec, Canada, H3G 1A4
- Recruiting
- Montreal General Hospital - McGill University Health Centre
-
Contact:
- Mark Ware, MRCP(UK)
- Phone Number: 42784 514 934-1934
- Email: mark.ware@mcgill.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Idiopathic (primary) OA of the knee as defined by American College of Rheumatology criteria
- Age ≥50 years
- Numerical Rating Scale (NRS) Pain intensity score ≥ 4 (on a 0-10 scale)
- Stable medication and treatment regimen
- Open to Canadian Residents only
Exclusion Criteria:
- Pregnant/nursing
- BMI >39kg/m2
- Secondary causes of OA
- Stage IV OA of the knee
- Significant other cause of pain (e.g. fibromyalgia, CRPS)
- Significant cardiac, neurological, psychiatric or respiratory disease
- Joint infiltration in 30 days prior to trial or during study
- Positive urine screen for THC
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CanniMed™ DPF-I Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation (DPF) with a potency specification similar to CanniMed™ 22·1 product, of 21.9% w/w total THC and 0.8% w/w total CBD is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
Experimental: CanniMed™ DPF-II Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as the CanniMed™ 15·5 product, of 15.0% w/w total THC and 5.0% w/w total CBD is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
Experimental: CanniMed™ DPF-III Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as CanniMed™ 9·9 product, of 9.0% w/w total THC and 9.5% w/w total CBD is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
Experimental: CanniMed™ DPF-IV Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 4·10 product, of 3.8% w/w total THC and 10.0% w/w total CBD is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
Experimental: CanniMed™ DPF-V Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 1·13 product profile of 0.6% w/w total THC and 13.0% w/w total CBD is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
Placebo Comparator: CanniMed™ DPF-P Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of ethanol extracted DPF-V, reducing the potency profile to <0.3% w/w total THC and <0.3% w/w total CBD (comparable to the threshold levels described for "industrial hemp", as per the Canadian Industrial Hemp Regulations (SOR/98-156), is vapourized and inhaled by study subjects.
|
Cannabis sativa L. subsp.
indica, variety indica blends of flowering heads that have been air-dried, milled, destemmed and fine ground, stored in glass vials with aluminum caps in 100 mg dose size.
Other Names:
Volcano® Medic vapourizer is licensed for medical administration of cannabis in Canada March 2010 (Licence No. 82405). The contents of a vial of drug product formulation will be transferred to the Volcano® Medic's filling chamber (sample-holder) equipped top and bottom with fine wire mesh to retain the finely ground material. The filling chamber will be placed atop the main body of the unit and then have a, 12.5 L, heat-resistant Medic Valve balloon affixed. Active components are vapourized at 190 °C. The ensuing vapour is captured in the balloon and inhaled by the study subject using a standardized inhalation technique. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total pain reduction of vapourized cannabinoids with varying degrees of THC/CBD ratios in patients with painful OA of the knee.
Time Frame: 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes post-dose
|
The main efficacy endpoint is pain reduction, calculated as a change in pain intensity (VAS pain intensity) following each exposure.
A Total Pain Reduction (TOTPAR) score is calculated from repeated VAS pain scores taken immediately before (baseline) and every 15 minutes after exposure for the first hour then half-hourly for the remaining two hours after treatment exposure (treatment).
The treatment VAS pain intensity scores are then subtracted from the baseline VAS pain intensity to generate a pain relief score for each time point.
The sum of pain relief scores from each time point is used to generate a 3-hour Total Pain Reduction (TOTPAR-3) score for each exposure.
|
0, 15, 30, 45, 60, 90, 120, 150, 180 minutes post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain, stiffness, physical, social and emotional functional outcomes of vapourized cannabis with varying degrees of THC/CBD ratios in patients with painful OA of the knee.
Time Frame: Up to 6 weeks
|
Pain and functional outcomes will be measured using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). The WOMAC Osteoarthritis Index is a 24-item instrument that assesses the three dimensions of pain, disability and joint stiffness in studies of knee and hip osteoarthritis. The WOMAC Osteoarthritis Index will be completed by the subject at Visit 2-8. |
Up to 6 weeks
|
Pharmacokinetics profile of 7 plasma cannabinoid metabolites from vapourized cannabis of differing cannabinoid profiles in patients with OA.
Time Frame: 0, 15, 30, 60, 120 and 180 minutes post-dose
|
Pharmacokinetic analysis encompasses an assay validated for: Δ9-tetrahydrocannabinol (THC); 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (11-nor-Δ9-THC-9-COOH); 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC); cannabinol (CBN); cannabidiol (CBD); and qualified for: Δ9-tetrahydrocannabinolic acid (THCA); cannabidiolic acid (CBDA). Blood will be taken prior to inhalation (T = 0) and at 2, 30, 60, and 180 minutes after each exposure for pharmacokinetic assessments of plasma cannabinoid levels. These intervals have been used to evaluate PK of vapourized cannabis in healthy volunteers (Abrams, et al., 2007). |
0, 15, 30, 60, 120 and 180 minutes post-dose
|
Changes in blood pressure from baseline
Time Frame: Up to 7 weeks
|
Resting/sitting and postural change in blood pressure are assessed at screening and at each subsequent clinical visit where the interventions are used to gauge changes and acute or sustained changes during the course of treatment.
Sitting and postural change in BP are taken at 0, 30, 60, 90, 120, 150, and 180 minutes post-dose.
|
Up to 7 weeks
|
Changes in heart rate (HR) from baseline
Time Frame: Up to 7 weeks
|
Sitting heart rates are assessed at screening and at each subsequent clinical visit where the interventions are used to gauge changes and acute or sustained changes during the course of treatment.
Sitting HR is taken at 0, 30, 60, 90, 120, 150, and 180 minutes post-dose.
|
Up to 7 weeks
|
Blood chemistry - liver function
Time Frame: Up to 7 weeks
|
Blood is taken at screening, and then for each clinical visit where the interventions are used at T = 0 (prior to inhalation) and at T = 180 minutes (end of study visit) for aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT).
Inclusion criteria for candidates is AST < 3X normal (normal = 5 - 40 units per litre of serum).
Change from baseline at screening and per visit with intervention will be assessed for short term liver changes following a single exposure to differing levels of inhaled THC and/or CBD.
|
Up to 7 weeks
|
Blood chemistry - renal function
Time Frame: Up to 7 weeks
|
Blood is taken at screening, and then for each clinical visit where the interventions are used at T = 0 (prior to inhalation) and at T = 180 minutes (end of study visit) for serum creatinine.
Inclusion criteria for candidates is serum creatinine < 133 μmol/.
Change from baseline at screening and per visit with intervention will be assessed for short term renal changes following a single exposure to differing levels of inhaled THC and/or CBD.
|
Up to 7 weeks
|
Hematology - hematocrit level (complete blood count)
Time Frame: Up to 7 weeks
|
Blood is taken at screening, and then for each clinical visit where the interventions are used at T = 0 (prior to inhalation) and at T = 180 minutes (end of study visit) for hematocrit level (or CBC).
Inclusion criteria for candidates is CBC > 35%.
Change from baseline at screening and per visit with intervention will be assessed for short term hematological changes following a single exposure to differing levels of inhaled THC and/or CBD.
|
Up to 7 weeks
|
Cannabinoid urine analysis at screening and for washout confirmation
Time Frame: Up to 7 weeks
|
Urine analysis (THC = 50 mg/mL) will be performed at each clinical visit to gauge cannabinoid clearance prior to the interventions and to ensure that washout between interventions is maintained as each dose should not produce a sustained 1 week urine result.
|
Up to 7 weeks
|
Psychoactive adverse events
Time Frame: Up to 6 weeks
|
A Psychoactive Adverse Event checklist will be administered by the Research Nurse to the participant to report on any changes in their emotional state (such as anxiety, panic, paranoia, depersonalization, mood alteration and altered perceptions etc) every 15 minutes after exposure for the first hour then half-hourly for the remaining two hours.
|
Up to 6 weeks
|
Patient global rating of preference for each cannabis preparation.
Time Frame: Up to 6 weeks
|
Patient global rating of preference for each cannabis preparation will be measured using a VAS (drug liking 0: Do not like at all; 100: really like a lot) after each exposure, and a global ranking after all six exposures have been completed.
|
Up to 6 weeks
|
Visual Analog Scale (VAS) feelings of drug effect
Time Frame: Up to 6 weeks
|
The VAS for feelings of drug effect is a horizontal line measurement of 100mm with Anchors of 0 = not high at all and 100 = most high ever. Subjects mark their Feeling of Drug Effect by placing a vertical line through the horizontal line to indicate how "high" they are feeling NOW. The VAS for Feelings of Drug Effect will be completed by the subject at each intervention visit; taken at 15 minute intervals after exposure for the first hour then half-hourly for the remaining two hours. |
Up to 6 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mark Ware, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Principal Investigator: Mary Lynch, MD, Queen Elizabeth II Health Science Centre
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PPS001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Osteoarthritis, Knee
-
LifeBridge HealthMicroPort Orthopedics Inc.; Rubin Institute for Advanced OrthopedicsRecruitingKnee Osteoarthritis | Osteoarthritis, Knee | Knee Pain Chronic | Arthropathy of Knee Joint | Knee Disease | Osteoarthritis Knees Both | Osteoarthritis Knee Left | Osteoarthritis Knee RightUnited States
-
University Hospital, Clermont-FerrandSanofiCompletedKnee Osteoarthritis (Knee OA)France
-
Joseph E. BroylesCompletedDegenerative Lesion of Articular Cartilage of Knee | Degeneration; Articular Cartilage, Knee | Unilateral Primary Osteoarthritis of Knee | Osteoarthritis Knee
-
The Hong Kong Polytechnic UniversityCompleted
-
Federal University of São PauloCompletedKNEE OSTEOARTHRITISBrazil
-
Jiangsu XinChen-Techfields Pharma Co., LTD.Completed
-
Novartis PharmaceuticalsRecruitingSymptomatic Knee OsteoarthritisUnited States, Spain, Hungary, Argentina, Germany, Slovakia, Czechia, Belgium, Romania
-
University of BathUniversity of Oxford; 3D Metal Printing Ltd; Versus ArthritisRecruitingMedial Knee OsteoarthritisUnited Kingdom
-
Max Biocare Pty. Ltd.Completed
Clinical Trials on Cannabis
-
University of California, San DiegoRecruiting
-
Germans Trias i Pujol HospitalIstituto Superiore di Sanità; Fundació Institut Germans Trias i PujolCompletedHealthy Subjects | Cannabis UseSpain
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
Khon Kaen UniversityEnrolling by invitationSpinal Cord InjuryThailand
-
Centre hospitalier de l'Université de Montréal...Completed
-
Rambam Health Care CampusCompleted1- Cancer Patients During Chemotherapy Treatment | 2- Use of Cannabis Comparing to Control Without Cannabis UseIsrael
-
Bayliss J. Camp, PhDRecruitingDriving Impaired | Cannabis SmokingUnited States
-
University of California, San FranciscoTobacco Related Disease Research ProgramRecruitingTobacco Use | Cannabis | Cardiovascular Risk Factor | Nicotine Dependence | Cigarette Smoking | THC | Nicotine Withdrawal | Cannabis Smoking | Cannabis Use, UnspecifiedUnited States
-
New York State Psychiatric InstituteSuspended
-
Center for Medicinal Cannabis ResearchCompleted