Questions remain about whether the early clinical trial will answer necessary questions.
Australian researchers have embarked on a small early trial of a topical cannabidiol to treat painful joints in patients with rheumatoid arthritis.
And while the Australian Rheumatology Association president Dr Sam Whittle has described it as a positive step forward, he cautioned that more study must follow to address efficacy.
The phase 2 open-label, single-arm clinical trial is a joint venture between Western Sydney University’s National Institute of Complementary Medicine and Australian biotechnology company Oz Medicann Pharma (OMG Pharma).
OMG Pharma, which manufactures the CBD salve, is funding the project. The active pharmaceutical ingredient in the topical roll-on study medication treatment is CBD derived from the cannabis sativa plant.
The salve is formulated with 4.64% CBD and the remaining 95.36% of the salve is made up of beeswax, coconut oil, cocoa butter, menthol crystals and a range of essential oils, to assist with the delivery of CBD to the affected joints.
National Institute of Complementary Medicine chief investigator Associate Professor Carolyn Ee said they were looking to recruit 20 patients to the four-week trial. So far two patients had joined the trial, she said.
Being a single-arm trial, everyone will receive the intervention and serve as their own control.
They will use the roll-on CBD salve at least twice daily, and additionally as needed; and be asked to record all daily medications including pain medications and the roll-on, as well as details of any side effects.
Participants will also be required to complete questionnaires and take part in physical examinations, including a count of swollen and tender joints.
Professor Ee said rheumatologists Professor Nicholas Manolios, Professor Peter Wong, and Dr Beverly Ng from Westmead Hospital’s Rheumatology Department had been actively involved in developing the study.
“They all had a big input in writing the protocol and choosing the outcome measures. So they’re all investigators on this trial,” said Professor Ee.
Professor Ee told Rheumatology Republic that early anecdotal evidence suggested topical CBD may have beneficial effects on pain and function in arthritis.
“This is really a very preliminary study to see if we can show that there is some kind of pre-post difference, because if there isn’t, there’s not really much point in going forward and doing a bigger trial,” she said.
“But absolutely, if we do see that it does make a difference to pain and function, then I think the company [OMG Pharma] is very interested in looking at a randomised, double, blind, controlled trial – the gold standard.”
Professor Ee said topical CBD applied directly to the skin over painful joints potentially had several advantages, including few side effects.
“CBD does not contain any of the compounds in cannabis that can cause people to feel ‘high’, so using this medication will not affect a participant’s mental state,” she said.
The trial is open to adults with rheumatoid arthritis that is not well controlled on existing medication; who are experiencing joint pain in at least four joints; who have not used medicinal or recreational cannabis for the past three months; and who can travel to Western Sydney University Westmead campus for two visits over four weeks.
More information is available on the participant information sheet.
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Professor Ee told RR that the endpoints of the study were pain and function.
“We’ve got pain using a visual analog scale, health related quality of life, the DAS-28, which also incorporates things like the tender joint count and swollen joint count; and general, physical, mental and social wellbeing as well,” she explained.
“We are doing markers, so CRP and ESR and patients fill out a daily medication diary, and obviously we’re tracking any adverse events throughout the trial as well.”
She said they were expecting the effects to “happen quite locally, because we know that there are cannabis receptors in joints and under skin, so we’re anticipating that the majority of the effect will actually happen quite locally by acting on those local receptors”.
“I’m expecting to see some kind of improvement in pain and function over the four weeks,” she said.
“I’m expecting to see some kind of signal. I guess the next step is really to understand, is this placebo effect, the fact that someone’s rubbing something over their hands and focusing on something that could possibly improve their pain and function?
“I think the next step would really be to do this in a controlled fashion.”
Australian Rheumatology Association president Dr Sam Whittle told Rheumatology Republic it was positive to see a trial in the medicinal cannabis space, even if it was a small and very early study.
“In our position statement, we say very clearly that we recognise the community interest in this [medicinal cannabis] and the lack of existing evidence,” he said.
“Therefore, we encourage the performance of high-quality clinical trials to establish an evidence base for these treatments that are already in the marketplace. So to the extent that this is an example of a research study being done in this space, in our patients, then that’s, I think, a step in the right direction.
“It’s an unusual situation with these cannabinoid interventions in that the commercial determinants of health have meant that we’ve ended up with drugs in the market well before there’s been any evidence to suggest that they’re safe or effective.
“So we’re now playing catch up. I think it’s interesting that the manufacturers of these products are now doing trials to generate an evidence base and I think that’s to be applauded, broadly speaking.”
Dr Whittle said he did have a concern about whether this type of trial design was the sort of thing that’s going to answer the questions that were important to patients.
“I recognise that this is an early phase study, and I don’t know what they’re planning after this trial, and whether this will lead to a placebo-controlled trial, for example,” he said.
“But we know that in trials of any intervention for chronic pain that where you don’t have a control group, you can’t really estimate efficacy at all, because you can’t account for placebo effects or for regression to the mean, which we know means that no matter what you do, people who enter a trial with pain will tend to improve, separate to whether or not the intervention is actually affected, and the way you control for that is by having a placebo control group.
“So one would hope that at some point there would be a placebo control trial, because that’s really the only way you can estimate efficacy.
“But if the intention of this trial is as a sort of proof of concept and to get some initial data around safety and tolerability, then I think that’s a step forward, but it also speaks to the incredibly slow arc of getting to the end point of having enough information to advise our patients properly about these expensive products that are already in the market.
“And if this is step one of a series of trials that are going to ultimately lead to a larger scale placebo control trial, then we’re looking at some years before we have those answers. And that’s, of course, a source of frustration for consumers and clinicians alike.”
Dr Whittle said it was reasonable for rheumatologists, as both a scientific community and a community of practice, to expect there is follow through with bigger trials across the entire medicinal cannabis industry more broadly, outside this particular trial.
“We’re still craving the large-scale trials that will provide us with a sort of robust scientific data that we can actually use to make good decisions with our patients,” he told RR.
“And we’re not the only ones crying out for this. It’s the patients as well.
“We know that up to a third of people with rheumatoid arthritis have persistent pain despite excellent anti-inflammatory therapies being available. And so there’s a huge unmet need here.
“If there is benefit for this population, then we need to find out. And the sooner we can find out, the better.”
Oz Medicann Pharma CEO and Founder John Leith said the company was proud of its longstanding research engagement with NICM.
“NICM’s reputation as a leader in this field solidifies the vital work we are doing in ensuring medicinal cannabis treatments are science backed,” he said.
“We’ve worked with NICM for a long time to come up with the best solutions that can help chronic pain sufferers worldwide, as well as other conditions such as insomnia.”
