A team of scientists led by Dr. Sean Dukelow of the University of Calgary is looking to add a new treatment to help stroke patients recover better from motor impairments. CAMAROS is a multicenter clinical trial to repurpose the use of Maraviroc drug in post-stroke patients undergoing rehabilitation treatment. Dr. Dukelow is working with teams across 8 locations in Canada to conduct the clinical trial.
More than 400,000 Canadians are living with long-term disability from stroke and this number will likely double by the year 2037. Motor impairments are one of the most frequent side effects of stroke related disabilities and depending on the extent of stroke deficits, patients require short or long-term rehabilitation treatments and every so often rely on assistance in going about daily tasks or movements.
“In the past 20 years, any treatment by way of drugs given to stroke patients have primarily been to prevent a recurrence of a stroke and/or administered medications within the first 24 hours to remove the clots that may occur as a result of the stroke,” says Dr. Sean Dukelow, Associate Professor, Department of Clinical Neuroscience, University of Calgary and Medical Director, Stroke Rehabilitation for the Calgary Stroke Program. “To date, there are no drugs proven to treat or improve a patient’s post-stroke recovery for motor impairments given outside the first few hours post-stroke.”
The counterproductive gene and the CAMAROS angle
CCR5 is a chemokine receptor and part of the G protein-coupled receptor (GPCR) that acts as a protein on the surface of white blood cells affecting our immune response. The CCR5 is a co-receptor for human immunodeficiency virus (HIV) which aids the virus to infiltrate and infect the immune cells. Scientists across the globe have been widely studying a potential treatment for HIV by blocking CCR5 using an antibody or a receptor antagonist.
Researchers have also found that lack of CCR5 receptors or use of pharmacological blockers of CCR5 could potentially help in faster learning and recovery from brain injuries.
Dr. Dukelow assessed the generalizability and transferability of this knowledge to explore its possible applications in a drug format. More specifically, in its extension to stroke patients with motor disabilities who are in the first few weeks of their in-patient rehabilitation therapy.
This is when he and his colleagues stumbled upon an existing drug Maraviroc (Celsentri), the drug that is being investigated under this clinical trial. Maraviroc is a CCR5 antagonist or entry inhibitor and according to Dukelow it is the perfect solution to test if there is a significant improvement in a stroke patient’s upper or lower body extremities.
The Canadian Maraviroc Randomized Controlled Trial to Augment Rehabilitation Outcomes After Stroke (CAMAROS) study is a randomized, placebo-controlled, blinded phase II trial that will evaluate the efficacy of coupling Maraviroc (Celsentri) with exercise rehabilitation.
The clinical trial
CAMAROS will be a multi-center trial spanning across 8 sites in Canada with approximately 120 patient participants.
The participants will be administered either the drug or the placebo in a double-blinded trial format across multiple locations over a period of 6 weeks and be monitored for a period of 3 months. The team will use the Fugl-Meyer test to measure the upper extremity motor assessment score for the impairment and use the 10-meter walking test to measure their lower extremity impairment.
The candidates selected for the trial will be adults aged 18 and over, who are undergoing in-person rehabilitation at the time of administering the first dose and must experience some form of motor impairment in either their upper or lower body due to the stroke.
Treatment could help vulnerable Canadians living with impairment after a stroke
“What we’re interested in is seeing if the drug can make a functional difference in their movement. For example, if we take two patients with similar post-stroke deficiency who are having difficulty picking up or holding a glass of water, the patient receiving the CCR5 receptor antagonist will hopefully show substantial change in their recovery and develop the ability to pick and hold the glass of water as compared to the other patient.”
Dr. Dukelow further explains that they expect to see significant improvement in patients taking the Maraviroc drug for 6 weeks, whether they continue to be in-patient or get discharged and continue the medication while they complete their rehabilitation as outpatients should not affect the outcome.
“Repurposing an existing drug is very exciting,” commented Dr. Michael D. Hill, Professor, Departments of Clinical Neurosciences, Community Health Sciences, Medicine and Radiology at the University of Calgary. Hill is also the Medical Director for the Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services. “If the CAMAROS trial is successful, we’ll be able to help many more people who have neurological deficits after they have a stroke. The Stroke Clinical Trials Group will function as the co-ordinating centre for the trial.”
Attracting investment and more potential projects in Canada
“Incredible innovation is happening in Alberta and across Canada, and the CAMAROS clinical trial is a great project that is shining light on the expertise available here, the life sciences clusters across different provinces, academic and health institutions, as well as Canada’s strengths in having several clinical trial site availabilities across provinces to conduct a multi-center clinical trial,” said Andrew MacIsaac, CEO, Applied Pharmaceutical Innovation (API).
“CAMAROS is funded by a US-based organization, and we’re attracting foreign investments directly in Canada. We want the industry and the organizations that are interested in stroke and stroke recovery to know that Canada is a great place for life science commercialization. We have the knowledge, experts, talent and the infrastructure in place to take the research to its next steps through clinical trials,” explains Dr. Dukelow.
When asked if he would like to say something to the patients and their families, Dukelow mentioned, “We’re actively looking to find improvements for people who have suffered a stroke and we spend every day trying to do better by them. This truly is about helping people to have a higher quality of life. That is what motivates us to do this work.”
Once Dr. Dukelow and his team get the final go-ahead by Health Canada, they will start recruiting patients for the Calgary center this April and slowly extend the trial to other locations that includes Dalhousie University (Halifax), Parkwood Institute (London), Memorial University of Newfoundland (Saint John’s), Sunnybrook Health Sciences Centre (Toronto), Toronto Rehabilitation Institute – University Health Network (Toronto), University of British Columbia & GF Strong Centre (Vancouver), and Riverview Health Centre (Winnipeg).