That’s what some Sunnybrook scientists are questioning, and now investigating in a clinical research study to enhance bone fracture repair.

The “magic pill” in this case is a daily medication already scientifically tested and well established in clinical use known as lithium carbonate.

With timed administration at very low doses, lithium carbonate has been shown to enhance bone repair, and now, orthopaedic clinical researchers are testing it in injured patients with fractures.

The Sunnybrook-led study – Lithium for Fracture Treatment (LiFT) – is a randomized controlled multi-centre clinical trial investigating if lithium can improve long bone fracture healing in healthy patients from 18 to 55 years of age, who have a shaft fracture of the femur, tibia/fibula, humerus or clavicle. Participants take the medication for just two weeks starting 14 days after the fracture or surgery.

“Fracture healing in adults typically takes several weeks to months to heal – and in up to 10 per cent of cases, it can fail to heal completely despite appropriate treatment,” says Dr. Diane Nam, an associate scientist with the Holland Bone and Joint Research Program and orthopaedic trauma surgeon at Sunnybrook.

Dr. Diane Nam, Principal Investigator on the LiFT trial.

“Sustaining a fracture significantly impacts an individual’s function, such as the ability to work, drive or physically parent young children. We’re talking not only about the long time to heal bones, but don’t forget the pain and negative impact on a patient’s quality of life and mental health. If we can show that this safe and inexpensive ($1/a day) therapy works, it can potentially have a huge impact to globally change how we manage fractures.”

Dr. Nam was involved in the scientific research from “lab bench to patient bedside”. She led the team as its principal investigator in conducting the pre-clinical work and in translating the research through to the current clinical trial.

The first few patients in the initial pilot clinical trial showed a reduction in pain with the use of lithium, with no impact on mental activity or mood. In order to keep the highest standards for clinical research, the current study is blinded, meaning that patients and the research team who will analyze the data do not know who is receiving the actual drug or a placebo pill in order to control for potential bias. 120 patients have been enrolled in the study to date.

The trial has sites at Sunnybrook, St. Michael’s Hospital, McMaster University Medical Centre, Ottawa Hospital and Royal Victoria Regional Health Centre, and is supported through Sunnybrook’s Centre for Clinical Trial Support (CCTS) and the Canadian Institutes for Health Research.

A research participant from the LiFT trial comes in for one of his check-in visits at the fracture clinic and to have x-rays taken.

The research team will analyze and compare X-ray result scores assessing for bone union where three of the four outer layers at the fracture site are bridged. They will also factor in how the research participants are functioning in their day-to-day life, including accounting for pain levels.

The research is also considering potential barriers to the acceptance of lithium therapy for the purpose of fracture healing, from both the perspective of patients and care providers. Of note, the dose of lithium being used in the study is so low (300 mg or one-quarter of the dose amount used for other applications) that it’s not detectable in blood work at 12 hours after taking it.

“This important clinical trial is one of many promising investigations that have resulted from collaborations between surgeons and scientists in the Holland Bone and Joint Program,” says Dr. Cari Whyne, senior investigator involved in the trial and the Susanne and William Holland Chair in Musculoskeletal Research at Sunnybrook Research Institute and University of Toronto. “This aligns with my research focus in clinically-translational bioengineering research aimed at maximizing function among those who develop musculoskeletal disease or disability.”

For more information about participating in the LiFT trial, contact lift@sunnybrook.ca

The post Igniting Discovery: Can we speed up bone healing? appeared first on Your Health Matters.

“We’re here to support our Sunnybrook investigators in their leadership of clinical trials,” says Gail Klein, operations director for the CCTS. “We’re their right-hand people; providing internal supports and a full-service package to make things easier for them, while also acting as a partner to the partners – that is, other trial sites worldwide.”

Sunnybrook has a strong history of leading clinical trials locally, nationally, and globally. CCTS has expertise in the management and coordination of single-centre, multicentre, national and international clinical trials and research projects across any therapeutic area at Sunnybrook.

“This is an incredibly exciting time to be part of the clinical trials team at Sunnybrook,” says Dr. Paul Karanicolas, medical and scientific director for the CCTS. “Across our institution, there is a renewed and growing focus on innovation leading us to the forefront of inventing the future of healthcare. Our work is not only advancing medical science—it’s directly impacting patient lives in meaningful ways.”

Have a Sunnybrook-led clinical research project in mind (or in the works)?

Contact the CCTS at: ccts@sunnybrook.ca

The post Igniting Discovery: Where researchers go to get their research projects off the ground appeared first on Your Health Matters.

Big sister Debbie has always been there for Cindy; this time, as they scurry through hospital corridors, a little late for their first appointment of the day.

Together, the siblings navigate traffic, banter over the long drive from Brantford, and keep on top of appointments. Debbie is a little on edge, given the circumstances. She takes her support role seriously, as she – more than most, due to her career in nursing – understands its importance to patients; her sister, in this case. Cindy, as a result, comes across as laid back and has an energetic spring in her step.

Despite having left early as they always do, the heavy fog and wet morning meant road conditions were heavier than usual. But nothing was going to get in their way…

Cindy is part of a clinical trial, or research study, that is testing an investigative drug therapy for the prevention of Alzheimer’s disease. It is one of many dementia research trials from the Brain Lab in the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Health Sciences Centre.

A volunteer participant for the study, Cindy is required to come in to hospital for regular visits – twice a month in her case, for now. This trip marked a year of visits; expected to continue another four years, for the duration of the five-year study.

Why would someone like Cindy – who shows no symptoms of Alzheimer’s disease – need or want to take that time to participate in such a research study?

When I first heard about this study, I knew right away I wanted to be a part of it. My mother had dementia, Alzheimer’s disease (AD). Seeing mom deteriorate mentally, it was difficult. She would have been in her late sixties, when she started manifesting confusion. She deteriorated; it was tough to see her go downhill. I wanted to learn what my risk was, to see if I could get more information, and what I could do about it”

Cindy Greatex,
clinical trial research participant,
68 years old 

Dementia is a term for several diseases that affect memory, thinking, and the ability to perform daily activities, with Alzheimer’s being the most common, contributing to about 60 to 70 per cent of dementia cases.

According to the World Health Organization, the illness gets worse over time and mainly affects older people. Having a family history of Alzheimer’s disease – in particular, if a biological parent or sibling has the disease – increases the risk of developing it.

As a part of the study, Cindy had the option to have her genes tested; she didn’t hesitate. The results showed that she has the strongest genetic risk factor for AD – which means she has a 15 times higher risk of developing the brain disorder than the average person.

As a medical doctor, Sunnybrook cognitive neurologist and brain scientist Dr. Sandra Black knows too well the devastating effects that diseases of the brain can have on patients, their quality and length of life, and their impact to families and loved ones.

Recognized internationally for her contributions to the diagnosis and treatment of vascular dementia, Alzheimer’s disease and stroke, Dr. Black has been compassionately providing care to patients and their families for most of her career, while working to advance research into what we know about the brain. This includes leading 88 clinical trials and training 110 trainees – new generations of clinicians and brain scientists, who have gone on to be leaders in cognition, stroke and dementia across the country.

While there are drug therapies available to help treat some of the symptoms of AD or other dementias (once those symptoms have already developed), there are limited medical options to address prevention, before the disease takes hold.

Yet Dr. Black has never been more optimistic.

Never before did we have the option or possibility of altering the pathway in which dementia develops. Now we’re actually looking at the pathology itself that leads to brain cell damage and cognitive decline. This is an emerging field and we’ve learned the sweet spot in preventing or slowing down Alzheimer’s disease is well before symptoms start.

Sandra Black,
Scientific Director, Dr. Sandra Black Centre for Brain Resilience and Recovery,
Sunnybrook Research Institute (SRI) and
Officer of the Order of Canada

She explains how the focus of therapies in their clinical trial research now is to intervene before the toxic processes behind the disease begin to form – a minimum of 10 to 15 years before symptoms kick in and “have a life of their own”, spreading in the brain.

“If we can do that, then you’re going to avoid it (dementia developing). It’s like stroke prevention: you get worked up, and put on prevention therapies, so you don’t have a stroke.”

The comparison should not go unnoticed, considering that she and her colleagues at Sunnybrook’s stroke clinic were one of the first to provide stroke prevention therapies in Canada in the 1990’s.

For the time being, volunteering to participate in a clinical trial is often the best option for patients like Cindy to access therapies that are not yet available “clinically”; in this case, a drug therapy in an effort to prevent or offset the very start of the disease process.

Receiving the drug, however, is not a guarantee as clinical trials are often randomized and blinded, which means volunteer participants are either selected for the drug therapy itself, or a “placebo” instead – the latter usually is just a saline solution – so Cindy and the research team don’t know which group she falls in.

“There has to be this placebo comparison in order for the study to be controlled, in order to validly test for any effects and differences – good or bad – of a drug being studied,” explains Halil Akbulut, clinical research coordinator in the Hurvitz Brain Sciences Program at Sunnybrook.

Without people like Cindy and her study support partner, we wouldn’t make any progress at all. They’re contributing to our understanding.

Cindy will continue to be closely monitored and tested for the duration of the study. Her sister Debbie is her “study partner”. In addition to providing a supportive role to Cindy, Debbie is part of her “team”, sharing any cognitive, physical or emotional changes she observes while outside the hospital setting. Changes to cognition can include thinking processes such as attention, learning and memory, language, remembering, reasoning, and problem solving.

If Cindy’s cognition or overall health declines, she will be pulled from the study. If it’s found that she was on the placebo, she will be offered the drug therapy as part of the agreement as a participant of the study. If she was on the drug arm of the study, she will continue to be offered it, for as long as she and her care team decide to use it.

I’m learning so much through this study, I’m learning how to eat better, how to sleep better, interacting more with people; so it’s giving me a lot of tools that I can put into place now while I’m going through the study, and I know it will make a difference in my life, to a better quality of life.

When asked if she had any advice to offer others who may be considering a clinical trial, Cindy added:

“If there are clinical studies available, sign up. It helps to find out as well genetically whether you have a predisposition – a higher probability of getting the disease – so there’s so many good points about being part of a study. I encourage people to find out if anything is happening in your community – I’m commuting myself – it’s worth the while to do that.”

The post Igniting Discovery: Can we stop dementia in its tracks, before it starts? appeared first on Your Health Matters.

It’s this highly-specialized setting within an academic health sciences centre that lays the foundation for clinical research – the study of health and illness in people – that drives discovery, innovation and learning in the field of critical care, at home and around the globe.

According to the Canadian Clinical Research Network, for the second year in a row, Sunnybrook has enrolled the highest number of patients in Canada in critical care-related trials funded by the Canadian Institutes of Health Research (CIHR).

Two current Sunnybrook-led clinical trials – on the cusp of discovery – are expected to produce evidence that will change the way critical care is practiced, and impact outcomes for critically-ill patients:

The world’s largest clinical trial in critical care:

Using antibiotics to prevent hospital-acquired infections before they happen.

Dr. Brian Cuthbertston, senior scientist in the Evaluative Clinical Sciences, Tory Trauma Research Program at SRI, is the international principal investigator for a number of global critical care studies and collaborations, including the SuDDICU trial.

Critically-ill patients who receive mechanical ventilation (assisted breathing) in an intensive care unit (ICU) are particularly at risk for hospital-acquired infections – these are infections that can develop while patients are in hospital receiving care, and are a major cause of illness, sometimes death, and increases to the costs of care.

While the evidence supporting the preventative use of antibiotics is strong, many health care professionals around the world don’t use this approach, out of a concern of the effects of antibiotic resistance – when antibiotics are no longer effective.

Led by SRI in Canada and the U.K., and by The George Institute in Australia, the SuDDICU  study – Selective Decontamination of the Digestive tract in Intensive Care Unit patients – is a large, randomized controlled trial and international research collaboration, that was first established in 2009.

The researchers wanted to test:

• whether using antibiotics to prevent infections increases the number of patients who get better and go home after being critically unwell, and
• whether using antibiotics in this way affects patterns of antibiotic resistance – when antibiotics are no longer effective – in the ICU.

“The preliminary results are not only promising, but also came as a bit of a surprise,” says Dr. Brian Cuthbertson, international principal investigator of the trial, critical care physician and senior scientist at Sunnybrook.

This research aims to give health care professionals and patients data on the benefits so they can make informed decisions about providing preventive antibiotics as part of care.”

Publication of the study results are expected in the near future – stay tuned to SRI Research News.

The clinical trial ranked #1 out of hundreds of thousands of Health Canada pandemic study grant applications:

Swapping intravenous (IV) sedative for inhaled sedative for patients on a ventilator in the ICU.

This trial is homegrown within Canada (and includes a single U.S. site), but its potential for global impact is not any less significant.

A dose of isoflurane is prepared, as part of the SAVE-ICU trial designed and led by Sunnybrook. The inhaled sedative – known for its use in surgeries – has been tested for use with patients in the intensive care unit, versus traditional sedatives given through an intravenous (IV) line.

The SAVE-ICU study – SedAting with Volatile Anesthetics Critically Ill COVID-19 Patients in the Intensive Care Unit – is a collaborative, multi-hospital, randomized clinical trial testing:

• whether inhaled volatile sedatives – a more widely available anesthetic commonly used in operating rooms – can replace sedative drugs that are typically delivered intravenously (by IV) for patients in the ICU with respiratory distress requiring ventilation; and
• whether patients recover faster with this form of sedation.

“In order to tolerate the uncomfortable procedure of being put on a breathing machine, patients require sedation or sleep-inducing medications,” explains Dr. Angela Jerath, lead principal investigator of the study, anesthesiologist, and a scientist in Evaluative Clinical Sciences at Sunnybrook. “At the beginning of the COVID-19 pandemic, these drugs were in short supply due to the high number of patients needing ventilators.”

The investigators will compare the impact that inhaled versus IV sedation has on outcomes important to patients with respiratory failure, their ICU clinical teams, and health resource use; this includes ICU and ventilator-free days, quality of life, delirium and hospital mortality.

Adds Dr. Jerath: “There has been some evidence to suggest that these (inhaled volatile) drugs may also have properties that reduce lung inflammation, which may speed up recovery and reduce the time patients spend on a ventilator.”

The investigators are also continuing to look for any elevation in risk between the two methods of sedation, but there has been no indication to stop in the last few years, with no adverse events showing.

“As the inhaled sedative doesn’t have to be filtered through the body like the IV sedation does, there are benefits for the lungs, liver and kidneys, for cancer patients, and with no particular concerns over IV sedation seen,” explains Eily Shaw, the research coordinator on the trial.

“When you turn the dose up/down with an IV drip, you need to wait for the body to process it first, and there’s also a considerable ‘wash out’ period after with patients coming off the effects from the sedative days or even weeks later. It can be a long time before they feel themselves again which can be confusing and sometimes scary.”

Although volatile (inhaled) anesthetics are not new (as a standard of care for surgeries), “their use still had to be studied in the context of the ICU because the type of person coming in for surgery is different than the patient who is ventilated due to respiratory distress in critical care,” says Eily.

At the study start in 2021, it was initially aimed at patients with a COVID diagnosis, but has since expanded to include any patient in the ICU with any kind of respiratory distress (lung failure) requiring sedation on a ventilator.

Dr. Angela Jerath, scientist and anesthesiologist in the Schulich Heart Program, is the lead principal investigator of the SAVE-ICU study.

The goal of this study is to determine if inhaled sedation should be a standard of care in the ICU as well,” says Dr. Jerath. “This can be done differently between hospitals (with different tiers of care), and would also ease the pressure on IV sedation stock, in particular during heightened times of need, such as a pandemic.”

With over 750 research participants over the four-year study period, it will take another year or two to assess the data. In the meantime, members of the research team like Eily are left humbled with their own anecdotal personal observations and sense of what it means:

I’m always buoyed by how thankful our participants and their families are to be involved in our research. For me, the human component is what makes the work we do particularly special. Our team certainly can’t take all the credit but it’s so massively rewarding to see patients when they get better and they look totally different at follow ups and are so grateful, we understand the importance of doing this.”

The post Igniting Discovery: Clinical trials changing the trajectory for the critically ill appeared first on Your Health Matters.

Since joining Sunnybrook’s Schulich Heart Program in 2014 as a clinical trial coordinator, Sulagna estimates she has met around 400 patients and their family members.

Together with her colleagues Mary Li and Sara Jabeen, the trio are part of the Schulich Clinical Trials unit that runs numerous investigational trials aimed at preventing, detecting and treating some of the most complex cardiac conditions.

It’s no small task. Sunnybrook’s Schulich Heart Centre currently has 32 trials running.  From ethics submission, legal contract, budget, recruitment, to consent and enrolment, data entry and management, audit, to follow-up visits, study completion, the role is both critical and, according to Sulagna, very fulfilling.

“There is a lot of trust placed in us, from both patients, their families and the clinical team,” says Sulagna. “Some of these trials can run up to more than ten years, with numerous in-person visits and tests. I really get to know patients and their loved ones.”

Underlying her work, and that of the research team, is the knowledge that heart disease is one of the leading causes of death in Canada.

From left to right: Sara Jabeen, Sulagna and Mary Li, members of the Schulich Clinical Trials unit.

“It’s gratifying to play a part in the clinical trials process. The entire heart team are so collaborative, with everyone having an open door and willing to hear our feedback. At the back of my mind is the knowledge that these trials will determine if new tests and treatment work and are safe. Lives will be truly be changed,” adds Sulagna.

Clinician-researchers, like Dr. Sheldon Singh, Lead of Clinical Trials Unit in the Schulich Heart Program, say clinical trial coordinators are the backbone of research at Sunnybrook.

“Clinical trial coordinators have a dual role of empowering Sunnybrook’s cardiologists to study cutting-edge technologies and drugs, while also working closely with patient participants to ensure they understand the implications and stay safe.  We are lucky to have a team that do a great job fulfilling these very important responsibilities,” says Dr. Singh.

For Sulagna, the highlight of her work has been the relationships she has built. She hears about patients’ milestones, like weddings, births and funerals.

“I’m playing a role within a highly collaborative team, and one that will ultimately help to improve cardiac care for patients. I’m very lucky,” says Sulagna.

The post Igniting Discovery: The role of clinical trial coordinators in Sunnybrook’s heart program appeared first on Your Health Matters.