Professor Philip Bath
Stroke Association Chair and Head of Stroke Medicine, and Acting Head of Cardiovascular Medicine, at the University of Nottingham
Philip Bath ran his first trial of glyceryl trinitrate (GTN) patches in 1994 while working at King’s College Hospital in London. He was investigating whether GTN, which has been used for decades to treat the heart condition angina, could be used to improve the recovery of stroke patients by lowering their blood pressure.
Eighteen years later, Philip is on the verge of finding out. His MRC-funded trial ENOS (Efficacy of Nitric Oxide in Stroke) is recruiting ahead of schedule and the results should be ready to publish in May 2014. While this might sound like a while away to some, to Philip he is on the final straight of a long journey.
“Like most clinical scientists I’d like my work to inform and ultimately change clinical practice. If ENOS is positive, it’s such an easy thing to implement,” he says.
Relieving the pressure
Strokes are caused either by the blood supply to the brain being blocked — by a clot — or by a blood vessel in the brain bursting. The damage to the brain kills a third of people within a year and leaves another third disabled.
Most patients who have suffered a stroke have raised blood pressure, and people with raised blood pressure recover less quickly and are more likely to die or have another stroke.
Finding an inexpensive and easy way to administer a blood pressure-lowering agent should therefore help patients and reduce the burden on the health service. GTN is converted into nitric oxide in the body, which lowers blood pressure by widening blood vessels.
“If anything is going to work, this drug has a really good chance. If there is a positive outcome, I would hope — given that it costs £6 per patient, is readily available and is easy to administer — that it could get into routine practice quickly,” says Philip.
ENOS is assessing the outcomes of 1,800 people given the patch within 48 hours of their stroke and comparing their recovery with 1,800 people who haven’t received the patch.
The full-blown study began in 2006 and, prior to that, Philip had carried out three preliminary trials in a total of 137 patients and an initial phase of the larger trial with 400 patients.
Philip says it’s become obvious in the years since ENOS started that the earlier an intervention can be delivered, the better. With this in mind, ENOS has also led to an unusual spin-off trial.
The RIGHT trial is the world’s first completed randomised controlled stroke trial done in an ambulance and has tested using GTN patches within 4 hours of a stroke by recruiting and treating 41 patients in the ambulance.
Regenerating the brain
Another focus of Philip’s research is looking at whether the brains of stroke patients can be encouraged to repair themselves.
There is evidence that stem cells from the bone marrow can renew tissue and cells elsewhere in the body, and it’s possible that they could become brain cells. Between 2006 and 2009, the MRC funded Philip to run a trial called STEMS-2, which attempted to track these stem cells to see if they ended up in the brain.
He and his team used a drug called G-CSF to stimulate bone marrow stem cells called CD34 cells to be released into the bloodstream around a week after a stroke. They then labelled these cells with particles of iron, injected them back into the bloodstream and then carried out brain scans to see whether they made it to the brain or not. Philip and his team weren’t expecting the CD34 cells to turn into new neurons to replace the ones damaged by stroke, but they might have motivated local stem cells to come and do the job.
While using G-CSF in this way was found to be safe, it was more difficult that Philip had envisaged to see the iron-labelled stem cells. In addition, the protocols involved meant that they couldn’t carry out the cell tracking on all 60 recruited patients.
“We’ve learned from this and are now developing a new protocol for a trial called STEMS-4. In addition, a colleague of mine is running the STEMS-3 trial which is focusing on patients who have had strokes months rather than days earlier.”
The next generation
All these trials mean that Philip has cut his time in the clinic from one in five weeks to one in seven. But maintaining links with patients is important to him:
“I feel like research makes me a more credible clinician — the fact that I’m seeing patients gives me an extra drive to help them.”
Philip’s research team has almost doubled in size in the past five years and he’s passionate about nurturing the next generation of clinician scientists.
“Training to be a researcher within a clinical environment has changed a lot. I had senior mentors who were very influential so I try to provide that for my junior colleagues.
“It’s great to see them flourishing. I’m really please to be helping to create the next generation of researchers.”
Updated August 2012