Clinical trial: a bit of science and medicine, simplified

Friday, March 26 2021, 1:24PM

I’ve been digging into the science behind the Etanercept treatment (I used to be a professional scientist and still have the research approach to any problem or question that I have. There’s a few links in this blog to reports which are freely available online and I’ve tried to find the ones that are an easy read without being too technical.

First: the problem.

In 2015, an estimated 394,000 people—199,000 males and 195,000 females—had had a stroke at some time in their lives, based on  data from the Australian Bureau of Statistics. In 2015, there were around 36,700 stroke events—around 100 every day.

While the median age for stroke in Australia is around 75 years, one in every four occurs in a person aged less than 65 years. Around 30 per cent of Australia’s more than 420,000 stroke survivors are of working age and around 40% of all stroke survivors report some form of disability. While stroke survival is improving (in part due to increased awareness by approaches such as F.A.S.T.), more people of working age are suffering from strokes and many consequently have to deal with some form of disability.

A recent blog post by a 22 year old indicates that being young and fit is no guarantee that a stroke wont happen to you.

 

Strokes can do more than damage a small area of your brain. A growing body of evidence suggests that strokes may result in persistent brain inflammation and that this may impair brain functional connectivity, resulting in of the post-stroke symptoms so many of us have to live with. This inflammation is caused by a naturally occurring molecule, tumour necrosis factor (TNF), in the brain. etanercept is a protein that potently and selectively inhibits the biological activity of TNF. It is already approved for use in treating rheumatoid arthritis and other inflammatory conditions. The problem is, getting it into the brain is tricky.

Second, the solution

The fluid inside your brain and spinal column is called the Cerebro-Spinal Fluid (CSF) and it’s kept isolated from the blood circulation by the Blood-Brain Barrier. This prevents many large molecules circulating in the blood  from passing into the CSF and potentially causing problems. So taking etanercept to treat rheumatoid arthritis won’t do anything for stroke symptoms because it can’t get to where it needs to be.

Perispinal injection is a way around this. The treatment is injected under the skin at the base of the neck and the patient is then positioned head down for a while. It was discovered during research on the effects of flying upside down that proteins can be transferred into the CSF via the brain’s venous and drainage vessels thus avoiding the problem of getting through the blood-brain-barrier. Researchers have used this to develop the perispinal injection as a way of “sneaking in the back door”

Although the treatment has been used and studied since 2006, action/inaction by the pharmaceutical companies holding the etanercept patents and an unhelpful attitude from the American Academy of Neurology in discouraging its members from participating in any trials, clinical studies to achieve registration have been thin on the ground. In 2015 a charitable trust, the Stroke Recovery Trial Fund, was established in Australia to garner community donated funds to research and trial new stroke treatments.  Founding member and director of the fund is Coralie Graham, who was the mother of a  patient who received the etanercept treatment in a US trial

The fund has been supporting trials on perispinal injection of etanercept  at Griffith University and elsewhere, with the ultimate aim of getting it approved for use in Australia and onto the Pharmaceutical Benefits Scheme (PBS). Funding from the Australian public has made possible the first formal controlled trial of perispinal etanercept on post-stroke patients.

 Third, the results

Even though clinical trials have not been widely conducted, there are many published reports that give some idea why the researchers are so excited by this new treatment.

Studies have reported improvements in chronic pain (felt constantly by one patient for 15 years post-stroke), improvements in gait, balance, vision, fatigue levels, spasticity, limb movement and seizures. Improvements have occurred in as little as 30 minutes post-treatment and the effects have lasted as long as the study follow up periods (months). If approved, this treatment promises to revolutionise the treatment and management of post-stroke symptoms in Australia and around the world. It also opens the door to the treatment of other neurological conditions besides stroke, which may be exacerbated by inflammation in the brain. (Think repeated concussions, head injuries caused by vehicle accidents, etc.) It may not work for all people or  for all brain injuries (much more research required to determine that), but it may certainly help a lot of us and it’s worth supporting, either with donations or by participating in a trial (as I’m doing). I may or may not get the Etanercept treatment, I have a 50:50 chance of getting it or a placebo. I (and the researchers involved) won’t know this until the trial is complete and I’ve had my final assessment. This is to prevent any possible bias creeping in to any assessment of my symptoms (willingly or unwillingly). If I get the placebo, I’ll have to wait until the treatment is approved for use in Australia and probably on the PBS .

I’ll let you know how it goes in a few months.

 

Some more links:

the Stroke Foundation’s Top 10 facts about Stroke

Summary of effects of etanercept

Brain Injury Australia

Stroke Recovery Trial Fund Facebook page

Other clinical trials related to stroke