Researchers at the Royal Adelaide Hospital (RAH) have tested a method of control of Parkinson’s disease symptoms that is safe and, for selected patients, provides more effective and consistent symptom control than oral medication.
The new skin infusion method provides 24-hour control of symptoms and is less invasive than surgical therapy.
A delicate balance
More than 80,000 Australians are living with Parkinson’s disease (PD). PD causes a slow degeneration of certain nerve cells in the brain that produce a chemical messenger called dopamine. This degeneration causes symptoms of impaired movement, such as tremor, slowness of movement, and muscle stiffness.
The most effective medication for PD is levodopa. Usually taken orally, levodopa helps to relieve motor (i.e. movement-related) symptoms of PD by maintaining dopamine levels in the brain. Levodopa needs to be taken regularly during the day to maintain motor symptom control.
As PD progresses, levodopa’s effectiveness becomes less consistent. Patients will begin to experience “off times”, when their symptoms are less well controlled and they can’t move as easily, alternating with “on times” when they have better symptom control.
Adding other medications or taking larger or more frequent doses of oral levodopa can help provide more “on time”, but can also result in side effects, such as restless involuntary movements, known as dyskinesias.
“You often have patients who have a good response to levodopa but it’s too short-lived, and when it’s working, they may have involuntary movements as well. So, it can be quite distressing for them,” said Associate Professor Thomas Kimber, head of the movement disorders clinical trial program at the RAH.
Continuous administration of levodopa throughout the day produces much more consistent levels in the blood stream, and much less ‘off time’.
This can be done via a gastrostomy tube, which delivers gel-form levodopa directly to the small intestine, from where it is absorbed into the blood.
“However, the procedure to insert the tube is invasive and it can be quite cosmetically challenging for people, having a gastrostomy tube protruding from their abdomen. The pump containing the gel is also quite heavy and bulky for them to carry around,” said A/Professor Kimber.
Other “device-assisted therapies”, such as deep brain stimulation surgery and subcutaneous apomorphine infusion, can help reduce “off time” and dyskinesias in PD, but are not suitable for and/or well-tolerated by all patients.
A less invasive solution
In a large multi-centre clinical trial, RAH researchers have tested a new method of levodopa delivery – continuous 24-h/day infusion into the skin.
Patients inserted a needle into the skin every few days, avoiding the need for surgery or the need to carry around a large bulky pump, while experiencing similar clinical benefits.
Safe, and more effective
After 12 weeks treatment, patients who used the skin infusion method experienced, on average, nearly two hours less ‘off time’ per day compared to those using oral levodopa. They also had nearly two hours more ‘on time’ without troublesome involuntary movements.
“It’s not good to be reducing off-time if you’re only going to be replacing it with on-time with troublesome dyskinesias,” said A/Professor Kimber.
“So, we are able to say that in patients who are inadequately controlled on their current medications and experiencing more than 2.5 hours of “off time” per day, subcutaneous infusion is more effective than optimally-dosed oral levodopa.”
“It’s still demanding for patients, having an infusion for 24 hours per day, but it’s certainly effective – and more effective than oral levodopa alone.”
Patients with the infusion method did not experience more frequent serious adverse events than those taking oral levodopa. However, the infusion group did experience more frequent non-serious and mild–moderate adverse events, such as skin irritation/inflammation at the infusion site. Adverse events led to 22 per cent of participants in the infusion group stopping therapy, compared to 1 per cent in the oral group.
“Compared to surgery, a subcutaneous infusion has relatively low upfront risks, so for those it doesn’t work out for, it’s fairly easy to discontinue and switch to a different treatment option” said A/Professor Kimber.
“This could be a significant advance; something new that we could offer patients instead of either oral levodopa or another device-assisted therapy,” said A/Professor Kimber.
The study is the latest from the Parkinson’s clinical trial program which has been running at the RAH for 20 years.
“We have one of the most experienced centres in Australia at participating in sponsored clinical trials of potential new PD therapies. We’ve got that track record,” said Professor Kimber.
This research was supported by Abbvie and by generous donors to the CALHN Neurology Unit, via the CALHN Health Services Charitable Gifts Board.