None listed
Conditions
Brief summary
People with chronic pain find that osteoarthritis can severely disrupt their life, robbing them of the pleasure of conducting simple daily activities. The present lack of effective medications means chronic pain is inadequately managed. Regular medications such as paracetamol are non-curative. Stronger medications, on the other hand, can cause drowsiness and/or unsteadiness. Furthermore, for opioids, the induced analgesia attenuates over time. The potential of cannabinoids for the treatment of osteoarthritis so far has not been fully appreciated. Published systematic reviews in the literature for the safety, efficacy and tolerability of cannabinoids in arthritis are scarce and have limitations that prevent meta-analyses. The aims of this study are: Stage 1: Determine the pharmacokinetics of CBD and PEA applied to skin Stage 2: Perform a randomised phase IIa double blind, placebo-controlled, three-arm cross-over study to examine the tolerability and efficacy of CBD and PEA in osteoarthritic joint pain. This research has been initiated by Prof Nicholas Manolios, Head of Department of Rheumatology, Westmead Hospital. This research has been funded by the Westmead Research Foundation. The funding body has no input into conduct of the research.
Interventions
Stage1: Dose finding study involving 2 visits. The patient with osteoarthritis will be given cannabidiol (CBD) or palmitoylethanolamide (PEA) in cream form over an affected painful joint, similar to Voltaren gel. Bloods will be taken to find the optimal dose using pharmakokinetics HPLC studies. The patient will have bloods taken 5 times over the course of Day 1 (including baseline) and return for 1 blood sample on Day 2, all up providing 6 blood samples for HPLC studies. The starting doses are 6
Stage1: Dose finding study involving 2 visits. The patient with osteoarthritis will be given cannabidiol (CBD) or palmitoylethanolamide (PEA) in cream form over an affected painful joint, similar to Voltaren gel. Bloods will be taken to find the optimal dose using pharmakokinetics HPLC studies. The patient will have bloods taken 5 times over the course of Day 1 (including baseline) and return for 1 blood sample on Day 2, all up providing 6 blood samples for HPLC studies. The starting doses are 62.5mg of CBD (3 subjects) or PEA (3 subjects). Doses are escalated as follows. If after the first dose 0/3 patients reach the target plasma concentration, then the dose of CBD and PEA will be doubled to 125mg. If 1/3 patients reach the target plasma concentration, then the dose of CBD and PEA will be increased by 50% to 94mg. If 2/3 patients reach the target plasma concentration, the dose of CBD and PEA will be increased by 25% to 78mg. After the second dose escalation, the same escalation strategy will be used. This will be repeated on newly recruited patients (unique cohorts of participants) for each dose escalation until the target plasma concentration of CBD and PEA is reached; 33.3ng/mL and 23pmol/mL, respectively. Dose escalations will be capped at a total of 5 escalations, to a maximum of 1000mg CBD or PEA applied to the skin. As cohorts for each dose are unique, no washout periods are required and the next dose can be given as soon as the next consenting subjects are recruited. Adherence monitoring is not required as staff will apply the cream on the patients in stage 1. Stage 2: Safety, efficacy and tolerability study for 26 weeks (once daily application). This stage is a three arm crossover, with each arm being 8 weeks followed by washout periods of 7days. Doses will be determined by Stage 1 for PEA and CBD arms. The third arm is placebo. Patients will also be given quality of life questionnaires to assess pain. Bloods will be taken to assess for safety measures such as liver function. A dosing diary will be supplied to patients and they will be asked to return empty cream bottles at study visits.
Sponsors
Westmead Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of OA defined by X-ray evidence of joint damage; 2. Age 30–90; 3. Disease duration of 2 years or more; 4. Continued pain in any of the knee, hip, hands or lower lumbar spine joints despite oral medications; 5. No previous use of oral or smoked cannabinoids for pain management; able to complete questionnaire; 6. Able to attend outpatient clinic at monitoring and follow-up time points.
Exclusion criteria
1. History of psychiatric disorder; 2. History of drug dependency; 3. Known sensitivity to cannabinoid agents; 4. History of epilepsy; patient pain explained by fibromyalgia; 5. Recurrent or recent malignancy; 6. Pregnancy or breastfeeding; 7. Change of pain medication in the preceding 4 weeks; 8. Severe renal or liver dysfunction (patient excluded if there is an elevation of baseline liver enzymes); 9. Concomitant medications: Prior or current cannabis use; current use of valproate, clobazam, topiramate, and/or rufinamide.
Outcome results
None listed