Very few researchers have endeavoured to do what Professor James McAuley and his team are about to embark on.
They’ve started a large, world-first trial exploring whether physiotherapy in combination with a drug can treat a rare chronic condition characterised by intense pain in parts of the body.
So far, definite treatment for ‘Complex Regional Pain Syndrome (CRPS)’ has eluded scientists for decades as its underlying mechanisms are hard to pinpoint.
“There’s a real unmet need for people in the community living with this really devastating pain condition for which there’s no treatment,” McAuley from the University of Notre Dame Australia said.
“It gets to the point that these symptoms become extremely distressing.
“So, we’re starting one of the biggest trials that may have been conducted globally, and we’re able to do that because we’re doing it as a tele-trial.”
McAuley joined Nursing Review in a conversation about this rare chronic condition and whether his team is close to finding the cure.
NR: What are the main symptoms of the condition and how can someone develop it?
JM: We’re investigating two promising treatments for CRPS. It’s a rare condition characterised by some horrible signs and symptoms that are very painful for the patient. So, for example, they may get a swollen hand or other peripheral parts of their body, although it’s usually the hand.
The main symptoms are intense pain and visible signs and symptoms, such as inflammation, swelling, changes in sweatiness, sometimes changes in the skin quality, colour and texture, and also changes in the quality of hair and nails.
Some people might get a hairier or less hairy limb, or nails that are either stronger or more brittle and crack. As time goes on, it becomes worse and worse. Unfortunately, there are very few treatments available for them.
The condition occurs most commonly following fracture or surgery and its incidence peaks between 50 and 70 years old. It’s a little bit more common in females than males, and we think that’s because [elderly] women tend to break bones a bit easier.
When someone falls, they often put their hand out to stop themselves from hitting the ground and may fracture their wrist. Then, they go to emergency and get some kind of slab on their hand, or maybe have an operation. And for most people, they recover very well. But about 3 to 5 per cent of people, when the slab or cast comes off, their hand doesn’t get any better but instead starts to get worse. It starts to feel worse over time and gets very, very painful.
It gets to the point that these symptoms become extremely distressing. And the treatments for it can either be ineffective or very intensive and marginally effective. So there’s a whole group of people in Australia with these symptoms and CRPS, for which evidence-based options are extremely limited. And hence, we came in with the trial.
How far has research progressed in finding a treatment for people with CRPS?
There’s so much we don’t know about this disease. One of the reasons is because it’s very rare. Therefore, researchers who investigate this usually only have one or two cases of people living with the condition in hospital clinics where people with CRPS invariably end up. So, we’re trying to recruit as many people as possible with this condition.
We’re starting one of the biggest trials that may have been conducted globally, and we’re able to do that because we’re doing it as a tele-trial. And that allows us to recruit more people, such as those who live in rural and remote parts of Australia, to engage with the clinical trials.
Covid has helped with normalising treatments on Zoom, for example, which has ended up being great for people with rare conditions because now they have access to specialists and also to clinical trials.
With this trial you’re hoping to create a new physiotherapy-based rehabilitation regime that aims to change how the brain processes information from the painful body part. Could you elaborate on that?
One of the things that we don’t know about CRPS is the mechanics behind it. If you look at the brains of people with CRPS in an MRI scanner, it’s pretty clear that they process information that’s coming from their affected body part in a different way than either their non-affected body part or people who don’t have CRPS.
It means that it opens up different types of interventions. One possible intervention is graded motor imagery, and we’re testing that. It includes mirror therapy and other modalities or interventions, such as laterality training.
Graded motor imagery is a treatment that’s been around for probably 20 to 25 years now and is used reasonably widely for people with CRPS. It’s only been tested in a couple of small trials, but what we’re doing in our trial is testing a more contemporary version of graded motor imagery.
What we’re testing is actually quite different to what has been tested in the past and what is used clinically. I suppose we’re using the latest scientific evidence to add to this intervention and make it a little more comprehensive.
The purpose is to try and change the way the brain is processing information that’s coming from the hand so that people can feel confident to move the hand or their body in a much more normal way, and start to be able to think about putting some weight on their hand and use their hand to do things that they haven’t been able to do in the past.
How does the condition progress? Does it ever go away by itself?
That’s a great question, and, unfortunately, like most questions to CRPS, we don’t have a lot of data to help us. Some very small studies with quite a number of limitations suggest that the recovery for CRPS is actually quite high initially. But for a proportion of people who don’t recover, say, within the first six to twelve months, continue to have pain and impaired function.
And we’re seeing those people because the trial’s already started. We have had over 3,000 inquiries about the trial. Not all of those people have CRPS, obviously, but many of those people have had CRPS for many years and are struggling. One of the things that has been very interesting as part of the trial in the last couple of months is seeing the unmet need in the community for people with ongoing symptoms of CRPS. We’re only recruiting people who have had CRPS for up to 5 years, but some have been having the condition for 30 to 40 years.
What are some of the treatments available to people with CRPS?
The most common intensive treatment is ketamine infusion, where people go to the hospital to receive it. So they might get ketamine infusion for over five to seven days, which would be a hospital stay. And that might give them some pain relief, but that is a relatively temporary solution. The pain often comes back after a few months, and then they return to the hospital for another ketamine infusion.
Obviously, not everybody can tolerate ketamine infusions because it also has a range of side effects. But this is the intervention that has the most evidence for it, even though it’s still done on very, very small trials. And I think that’s where our trial comes in.
So, it’s a burden for them to go to hospital all the time or to find treatment, even though it might be short-term.
There are two treatments we’re exploring in this trial. One is graded motor imagery which we just spoke about. The second one is whether or not a type of medicine can also help reduce pain intensity. We want to test whether or not that can help, combined with physiotherapy or on its own.
Unfortunately, we are restricted in what we can say about the medicine, but let’s just say it is a medicine that’s being repurposed in our trial. So it’s a medicine used for other conditions and has been around for quite some time. We think it might have some analgesic effects for CRPS. So we’re testing a 16-week course of this against a placebo.
Because it’s a rare condition, we want to get as much out of this trial as possible. That’s why we’re testing two trials within the one trial, if that makes it two treatments within the one trial.
Are you hopeful of the results? Or do you have some idea how this will work out?
Absolutely no idea at all, which is why we’re doing it. But as I said, in our previous studies, we found that these were promising interventions. It’s in its very early days, but it looked like there might be something there, but we cannot be sure.
We really hope that even by doing the study, we can help people with CRPS and maybe people with other chronic conditions and pain. For example, we will be starting a trial very soon for people with phantom limb pain and then hope to do another trial next year for kids who also develop CRPS.
We hope one of the benefits of this trial is that it does give people with CRPS some hope.
People with CRPS often feel like they’re being told that they’re just imagining it; that it can’t possibly be real because no tests have shown that there’s something wrong with their body. So they’re often made to feel like they’re making it up.
But it’s absolutely clear that everybody with CRPS has a real condition that is very distressing and affects their lives in many ways.
We are recruiting for the next couple of years in Australia and, again, nationally. So it doesn’t matter where you are; if you’re sitting in Alice Springs or up in Tennant Creek, Darwin or Melbourne, you can be part of this trial.