The combination of a new clinical trial and a tissue bank is innovating stroke care and research at the UK. Led by a multidisciplinary team of clinicians and scientists, the two studies aim to develop new treatments using existing therapies that protect brain tissue after a stroke, and to learn more about the physiology of the event.
The MAVARIC (Magnesium and Verapamil After Recanalization in Ischemia of the Cerebrum) clinical trial leverages existing standards of care and approved drugs to improve how the brain heals following a stroke. The related BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) study is developing a tissue bank of thrombi (stroke-causing clots) and distal and peripheral blood to examine the immediate molecular changes that occur at the stroke site. Both the MAVARIC trial and the BACTRAC study are the first of their kind.
The burden of stroke is especially severe in Kentucky, where it’s the third-leading cause of death (compared to fifth nationally) and occurs at earlier ages than in the rest of the country. Globally, stroke is the leading cause of morbidity and physical incapacity.
Despite the prevalence of stroke, current standards of care include only two potential treatments. One is a drug called tPA, which, if administered quickly enough, can break up the clot that caused the stroke. This treatment, however, has a limited window of opportunity – three to four and a half hours – and can exacerbate injury if delivered too late. The second treatment option is a thrombectomy, where the clot that caused a stroke is physically removed through a catheter inserted into the blood vessel. The therapeutic window for thrombectomy is much longer, sometimes up to 24 hours.
Even with the advances of tPA and thrombectomy, which can be highly effective in removing the cause of the stroke, neither therapy treats the injury inflicted by a stroke.
“Thrombectomy has become common and widely effective, but only 60 to 70 percent of patients will be independent in three months – so there is more to be done,” said Dr. Justin Fraser, director of cerebrovascular surgery at UK and one of the principal investigators of the MAVARIC trial.
Leveraging existing drugs and modalities
In the hope of improving stroke outcomes by treating the injured area of the brain, Fraser partnered with staff members of the UK Center for Advanced Translational Stroke Science, to look at repurposing existing drugs that, in combination with thrombectomy, could limit brain tissue damage and promote healing in stroke survivors.
After the clot is removed through the catheter, there’s immediate access to the site in the brain where the injury is occurring. UK takes existing therapeutics that already exist and puts them into the catheter immediately after removing the clot, so that the drug is delivered directly to the stroke-affected area of the brain.
Fraser began by repurposing an existing calcium channel blocker called Verapamil, which is mainly used to treat heart arrhythmias but is also FDA-approved for use to relax brain blood vessels that contract after a thrombectomy. Fraser noticed anecdotally that patients who received Verapamil during a thrombectomy had better outcomes than their imaging and symptoms would have predicted.
In a previous preclinical study and Phase I trial – the first in the world to pair thrombectomy with immediate, intra-arterial administration of a neuroprotective drug – Fraser found that intra-arterial delivery of Verapamil was safe. Furthermore, in cell culture and animal models of stroke, it was effective in preventing significant ischemia-induced injury. But they also understood that Verapamil alone wasn’t addressing the complex process of damage caused by stroke.
“There’s not going to be a single magic bullet in terms of drugs. When someone has a stroke, multiple pathways get activated and damaged. If you give a drug that addresses only one pathway, it doesn’t treat everything. So we need to try combining drugs,” Fraser said.
Researchers are working hard to identify new treatments and strategies to improve health and to understand the diseases that make us sick, but in order to succeed they need both healthy research participants and participants with medical conditions. Often, studies end because they don't have enough participants, leaving important questions unanswered. Continue reading about clinical trials »