Spencer Skaper is a Master of Science student at the University of Victoria and is leading a research project aimed at understanding how exercise improves blood flow to the brain in individuals with Down syndrome. This project is funded by the Canadian Consortium of Clinical Trial Training Platform-Clinical Trials Training Programs (CANTRAIN-CTTP) & Michael Smith Health Research BC Masters’ Studentship, which is a BC-based initiative with mentorship and support from the Cerebrovascular Health Exercise and Environmental Research Sciences laboratory under Dr. Kurt Smith, an expert in cerebrovascular health. Individuals with Down syndrome have lower blood flow to the brain, resulting in advanced aging and a higher risk of early Alzheimer’s disease and other cerebrovascular disorders. However, limited studies have demonstrated brain blood flow responses in a Down syndrome population, with fewer proposing early intervention strategies that preserve cerebrovascular function. Thus, this study aims to determine how moderate exercise affects brain blood flow in Down syndrome. We believe that aerobic exercise will improve brain blood flow in this population. These findings may be valuable for implementing early intervention strategies that preserve brain blood flow and limit early onset cerebrovascular complications in Down syndrome. The research findings could inform exercise recommendations to support brain health in Down syndrome, benefiting individuals, caregivers, and BC’s healthcare system. The results may also contribute to broader efforts in preventing cerebrovascular diseases in the aging Down syndrome populations.
Program: CANTRAIN
CANTRAIN & Michael Smith Health Research BC Internship/Practicum for Clinical Research Professionals Program 2023-24
Sherry Sandhu is a research assistant in the Department of Addiction Medicine and Substance Use Services at the Fraser Health Authority. She supports a research program called ‘Rahi’, which means ‘a companion along a path’ in Panjabi and Hindi. The principal investigator leading the project is Dr. Nitasha Puri, an addiction medicine physician and medical lead at the Roshni Clinic which is an addictions clinic tailored for the South Asian population in the Fraser Health region. Rahi aims to develop and test the feasibility of a culturally resonant intervention to treat substance use disorder among Panjabi men in British Columbia’s Lower Mainland. The first phase of this BC-based project was to design an intervention and was co-led and co-created with people who have lived and living experience using substances (PWLLE). As the team prepares for the next phase of testing the intervention, Sherry was awarded with a unique opportunity to gain clinical research that she can bring back to her team. Sherry was one of two recipients in BC to win the CANTRAIN & Michael Smith Health Research BC Internship/Practicum for Clinical Research Professionals Program 2023-24. The clinical research internship program is an initiative of the Canadian Consortium of Clinical Trial Training (CANTRAIN), a national platform funded by the Canadian Institutes of Health Research (CIHR). Michael Smith Health Research BC is a proud partner of CANTRAIN’s clinical research internship program. Sherry will use the important clinical research skills she gains through this award, to guide her team as they go on to test this community-led intervention. This research will be vital in changing the landscape of culturally tailored health care for South Asians across BC.
Patient- and family-centered approaches to informed consent in pragmatic critical care trials
Health Research BC is providing matching funds for this project, which is funded by the CANadian Consortium of Clinical Trial TRAINing Platform-Clinical Trials Training Program’s Doctoral Studentship 2023 Award
Individuals considering to take part in research must be given detailed information about the research and understand this information before voluntarily signing a form. This process is referred to as ‘informed consent’. The process does not seem to work in critical care when family members are approached to make decisions about research participation on behalf of their critically ill loved one. Family members often feel too overwhelmed and find the information hard to understand. As a result, individuals end up making uninformed decisions and patients get excluded from research that is needed to improve clinical care. Making informed consent processes better for patients and their families is difficult as we do not currently understand what matters to them, particularly to people from non-White racialized groups. This research tries to tackle this issue by understanding the needs of patients and their family members regarding informed consent in critical care research in Pakistan. To do this, we will use multiple different ways of obtaining information, including questionnaires, public surveys, interviews and group discussions. At the end of the study, we will propose new informed consent processes for two international research studies, operating in both Pakistan and British Columbia, that better suit the needs of South Asian patients and families. Recommendations will also be made to research studies globally to ensure informed consent works for all patients.
The study has been designed by a 2nd year PhD student based at the University of British Columbia, Dr Timo Tolppa, under the supervision of Dr Srinivas Murthy, a Clinical Associate Professor at BC Children’s Hospital, and in collaboration with a public engagement group based in Pakistan led by Dr Madiha Hashmi and Dr Arishay Hussaini.
End of Award Update – January 2025
Results
Our team co-created culturally relevant and patient-centered materials with members of the public to make clinical trials more understandable for patients in Pakistan. The materials were designed in the five main languages of Pakistan and include infographics, information sheets, audio recordings for illiterate patients as well as an animated video created by a Pakistani filmmaker: https://www.youtube.com/watch?v=dCZqm6hW0PM
Impact
The materials have helped researchers explain clinical trials to patients and their families, assisting them to make more informed decisions about trial participation. The new patient-centered materials have also been used to educate over 350 members of the public about clinical trials and their rights when it comes to research.
Potential Influence
Better understanding of clinical trials, public involvement in research and culturally appropriate study materials promote active engagement of patients in the decision-making process about health research. This ensures ethical conduct of clinical studies and may even encourage patient participation.
Next Steps
The next step is to evaluate whether the new research materials enhance patient understanding of trials, recruitment of participants into trials and the experiences of patients as well as researchers discussing potential trial participation.
Useful Links
The project is a collaborative effort with the Critical Care Research Group (https://zu.edu.pk/ccrg/) and the Patient & Public Involvement and Engagement group (https://zu.edu.pk/ppie/) both based at Ziauddin University in Karachi, Pakistan.
The NOVA-HIV Study: Reduced Dosing of the Nonavalent HPV Vaccine in Women Living with HIV (WLWH)
Human papillomavirus (HPV) is a sexually transmitted infection that causes cervical cancer. HPV vaccination and cervical screening are the best ways to prevent HPV and cervical cancer. Human Immunodeficiency Virus (HIV) is a virus that weakens the immune system. HPV vaccination and cervical screening are especially important for women living with HIV (WLWH), who have higher rates of HPV infection and are at greater risk for developing cervical cancer.
The primary goal of the NOVA-HIV study is to see if giving 2 doses of the nonavalent HPV vaccine provides as much protection as 3 doses. The objective of my graduate research within this study is to determine WLWH’s thoughts, feelings, and preferences in using self-collected swabs to test for HPV. Self-collected HPV tests may provide WLWH with an alternative and more acceptable method of screening for HPV.
This project will provide important information about the acceptability of new HPV testing procedures with the goal of making healthcare practices more comfortable and accessible for WLWH.
End of Award Update – February 2025
Results
My objective, as part of the NOVA-HIV study, was to determine the attitudes, perceptions, and acceptability of HPV self-sampling in women and people with a cervix living with HIV (WLWH) and to identify potential misconceptions and knowledge gaps surrounding this new screening methodology. At this stage in participant recruitment, we have collected questionnaires from 99 participants. In our preliminary analysis, HPV self-sampling is a highly acceptable screening method for this population and is viewed as safe and effective. However, we have also identified that many participants feel concern and uncertainty about the implications and next steps of receiving a positive HPV test result. These findings are crucial in creating strategies to make HPV self-sampling more equitable and accessible for WLWH.
Impact
As HPV DNA testing has been newly introduced within our cervical cancer screening program in BC, understanding its acceptability and implications for all populations, especially those most affected by HPV, is critical. WLWH are one such population. We have presented our preliminary acceptability data from this population and have outlined misconceptions and knowledge gaps surrounding HPV self-sampling to clinic staff involved in the care of WLWH, so they can better counsel and inform their patients about HPV-self sampling. These findings have been presented to clinician scientists, patient partners, and researchers at the Oak Tree Clinic research day at BC Women’s Hospital (a clinic providing specialized, interprofessional care to women and their families with HIV/AIDS in British Columbia).
Potential Influence
As of January 2024, HPV DNA testing and self-sampling have become the primary method of screening for cervical cancer in British Columbia; however, WLWH’s attitudes towards HPV self-sampling have not previously been investigated, despite the higher rates of cervical cancer and decreased access to cervical cancer screening within this population. Within BC, and as HPV self-sampling is implemented in other provinces/territories in Canada, it is especially important to consider WLWH’s acceptance of HPV self-collection as a method of screening for cervical cancer and to use this information to guide the development of specific resources to support and inform the community of WLWH about HPV self-sampling. We are currently planning an upcoming KT event to engage and inform the WLWH community of our exciting study findings.
Next Steps
We have submitted abstracts to share our findings at a national conference aimed at improving the health and well-being of people living with HIV in Canada, as well as a national meeting of women’s health care professionals. We also plan to host a dynamic community event for WLWH in Vancouver to address the knowledge gaps and misconceptions, and provide valuable educational resources based on these new and exciting findings.
Active Steps: Feasibility of a virtual intervention to promote active lifestyles in children with type 1 diabetes
Diabetes is one of the most common chronic conditions in children; in Canada nearly 30,000 children are affected by this life-threatening disease. Type one diabetes (T1D) is a condition that requires careful management, including frequent monitoring of blood glucose levels and lifelong insulin therapy. Regular physical activity is recommended for better blood glucose control, but fear of hypoglycemia (alarmingly low blood glucose levels) limits physical activity in these children. Few interventions have managed to meaningfully increase physical activity in children with diabetes. With this project, I will develop and test a virtual physical activity intervention. The project will take place in BC’s Interior, including rural and remote communities. It will be the first physical activity intervention for children with T1D in this region. The “Active Steps” project consists of five 45-minte virtual sessions over 12-weeks, addressing T1D related physical activity challenges. Participants will receive workbooks to work through with the physical activity counsellor during the sessions. They will also set their own activity goals and monitor them using a Fitbit Charge 5. To evaluate the program, we will look at how many kids join, how many finish and how well the virtual program works. We will also interview the children and their parents to see if they enjoyed the program. Children’s physical activity before and after the intervention will be measured. This study is an important first step to ultimately inform a larger randomized controlled trial that will aim to demonstrate the effectiveness of the intervention to increase physical activity.
The study will be conducted by Simran Gill, a PhD student under the supervision of Dr. Christine Voss. Simran is co-funded by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN-CTTP) and Michael Smith Health Research BC Doctoral Studentship.
Tributyrin Treatment and Prophylaxis of Recurrent Calcium Oxalate Nephrolithiasis
Kidney stone disease (KSD) is a condition where there are crystal deposits in the kidney, which affects around 10 percent of Canadians. These kidney stones can be painful to pass, and can cause lasting damage to the urinary tract. This places a large burden on the healthcare system and therefore there is motivation to further understand what causes kidney stones and how we can prevent them. The gut microbiome is a community of bacteria living in the gut which can produce substances such as short chain fatty acids (SCFAs). Individuals with KSD have a different makeup of their gut microbiome and lower amounts of these SCFAs compared to healthy individuals. Tributyrin is a supplement which can increase levels of SCFAs. Our data from animal studies indicate that tributyrin supplementation may be able to reduce kidney stone formation. This project aims to understand if tributyrin supplementation helps in prevention or treatment of those with KSD. This pilot clinical trial investigating tributyrin supplementation in individuals with KSD will be conducted in The Stone Centre at Vancouver General Hospital. It will provide a better understanding of the role of the gut microbiome in KSD, as well as explore another avenue of microbiome focused treatments for those with KSD.
Sarah Hanstock is funded for this project by the CANTRAIN-CTTP & Michael Smith Health Research BC Doctoral Studentship 2023 Award Program. This project will be conducted in The Stone Centre at Vancouver General Hospital under the supervision of Dr. Dirk Lange and Dr. Ben Chew. The Stone Centre is a translational research facility which has an international reputation for its care, treatment, and research of kidney stone disease.
End of Award Update – December 2024
Results
I successfully prepared and planned the necessary documents and protocols for our upcoming human trial with ethics approval submitted. Since we are in the early stages of this project there are unfortunately no results to share.
Impact
This research expands the knowledge gaps around the relationship between the gut microbiome and kidney stone disease.
Potential Influence
Upon completion this project may influence future treatment and prevention of kidney stone disease.
Next Steps
Since this project is still in its early stages our research group at The Stone Centre plans to continue this project to complete the human trial followed by knowledge dissemination of our findings.
Evaluating treatment and employment outcomes in adults with prescription opioid use disorder initiating methadone maintenance or buprenorphine/naloxone opioid agonist therapies in a pan-Canadian pragmatic randomized clinical trial
Since 2016, Canada has been facing a national opioid overdose crisis that continues to have devastating effects on people who use opioids, their families, and communities across the country. Opioid agonist therapies (OATs), such as methadone and buprenorphine/naloxone, are considered first-line treatment options for people with opioid use disorder (OUD) and have shown to reduce overdoses, cravings, and withdrawal symptoms. As a response to the ongoing opioid crisis, researchers with the Canadian Research Initiative on Substance Misuse (CRISM) launched OPTIMA, a 24-week pan-Canadian clinical trial that compared the effectiveness of methadone and buprenorphine-naloxone models among adults with OUD. The OPTIMA trial was conducted between 2017 and 2020 across four provinces in Canada, including British Columbia, where Dr. M Eugenia Socías led as the regional principal investigator. To learn more about the OPTIMA trial, visit here: https://www.optima-trial.com/.
One factor, employment, has shown to have many positive associations for people with OUD, but also present challenges for people on OATs. For instance, methadone typically requires daily attendance at a dispensing pharmacy, which can be a barrier to acquire or sustain employment. On the other hand, buprenorphine-naloxone has a more flexible take-home dosing option, which may improve patient autonomy. However, there is limited research on the differences between different treatment methods. My project aims to evaluate the bidirectional effects of employment and OATs on treatment outcomes among people with OUD, using the data from the OPTIMA trial. This research has been recognized and funded by CANTRAIN-CTTP & Michael Smith Health Research BC (Health Research BC) Master’s Studentship 2023 Award Program. The proposed research aims to further the equitable expansion of evidence-based policies and practices in BC, hopefully contributing to the improvement of addiction care and harm reduction for people who use opioids.
End of Award Update – January 2025
Results
Preliminary analysis revealed that part- or full-time employment is a strong positive factor linked to better treatment retention for individuals starting opioid agonist therapy (OAT) for opioid use disorder. Additionally, we discovered differences in treatment outcomes between methadone and buprenorphine/naloxone, depending on whether individuals were employed or not. These findings provide valuable insights into how employment status influences treatment success.
Impact & Potential Influence
As this project is ongoing, we hope to engage with key stakeholders, including community organizations, clinicians, and people with lived or living experience, to ensure the findings inform evidence-based practices. By highlighting the connection between employment and treatment outcomes, this research has the potential to advocate for policies that improve addiction care and harm reduction strategies in British Columbia, with broader implications throughout Canada.
Next Steps
Our next steps include sharing these findings on the relationship between employment and opioid use disorder through conference presentations, plain language summaries, and informational pamphlets targeted at researchers, clinicians, and people with lived or living experience. We also plan to collaborate with stakeholders to develop strategies for knowledge mobilization and advocate for policies and practices that improve both employment and treatment outcomes for people who use opioids.
The effects of dietary nitrate supplementation on exercise tolerance in patients with fibrotic interstitial lung disease
Health Research BC is contributing matching funds to support the CANTRAIN-CTTP & Michael Smith Health Research BC Doctoral Studentship 2023 Award Program. Olivia Ferguson is a Ph.D. student at the University of British Columbia. Olivia will be conducting a clinical trial in patients with chronic lung conditions under the supervision of Dr. Jordan Guenette at the Cardiopulmonary Exercise Physiology Laboratory at St. Paul’s Hospital in Vancouver, BC.
Interstitial lung disease (ILD) is a chronic progressive lung disease of either known or unknown cause, with a mean survival of only three years. ILD leads to progressive scarring of the lungs and debilitating reductions of exercise tolerance and functional abilities, which is strongly associated with reduced quality of life and mortality. Breathlessness and severely low oxygen levels in the blood are the hallmark features of ILD, which worsen with exercise. Unfortunately, very few effective and safe pharmacological therapies that target the lungs are available for ILD. Thus, preserving or enhancing muscle and heart function is essential to offset the progressive decline in lung health and for maintaining quality of life and independence. It is strongly advised that individuals with ILD undergo pulmonary rehabilitation, which is a structured exercise program; however, this may not be suitable for individuals who may not be able to handle strenuous exercise that can enhance muscle and heart function. Using nitrate in the form of concentrated beetroot juice, a safe and commercially available dietary supplement, may improve the delivery and efficiency of oxygen use at the site of exercising muscles. Orally ingesting dietary nitrate may improve the use of diminished oxygen availability rather than relying on external sources of supplemental oxygen, a common practice in ILD, which lacks real-world practicality. This novel therapeutic may allow individuals with ILD to reach exercise intensities sufficient for improving their overall exercise tolerance. If successful, it would enable them to sustain their functional abilities and engage in regular daily tasks, promoting independence and improved quality of life.
Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE)
Health Research BC is providing match funds for the Master’s Studentship 2023 Award, supported by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN). As part of my work, I will be conducting the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study. The ACCURATE, BC-based study is also funded by Genome British Columbia and Vancouver Coastal Health Research Institute (VCHRI).
Familial hypercholesterolemia (FH) is one of the most common genetic diseases, affecting 1 in 250 individuals and elevating the risk of early onset heart disease. About 1 in 14 individuals who have a heart attack under 60 years old have FH, but 99% of them were not aware of it before their heart attack. In British Columbia, over 85% of individuals with FH remain undiagnosed due to the lack of genetic testing, leading to missed opportunities for early intervention.
The ACCURATE study aims to investigate how genetic testing for patients hospitalized with acute coronary syndrome (ACS) can improve the diagnosis of FH, influence physicians’ treatment approaches, patients’ medication use, and ultimately reduce the disease burden for these patients.
The outcomes will contribute to understanding how genetic diagnosis influences patient care in acute cardiac settings, with the hope of influencing healthcare practices in the entire province. This will improve the health of British Columbians and enhance the reputation of BC as a leader in genomic clinical care.
End of Award Update – December 2024
Results
The ACCURATE study found that 8% of young acute coronary syndrome (ACS) patients with untreated LDL-C >4 mmol/L had a genetic diagnosis of Familial Hypercholesterolemia (FH). This is a prevalence 24 times higher than in the general population. Importantly, genetic testing reclassified 88% of these patients initially categorized as “unlikely” or “possible” FH to a confirmed diagnosis of “definite” FH. These findings show that genetic testing can identify FH in patients who would otherwise be missed using traditional clinical criteria alone. Additionally, 24% of patients were identified as having polygenic hypercholesterolemia. These patients did not carry variants in the known FH-causing genes but had a high LDL polygenic risk score (PRS), indicating that other genetic factors contribute to their elevated cholesterol and heart disease risk. Altogether, our current results highlight the value of both genetic testing and polygenic risk scoring in detecting, diagnosing and understanding FH in young high-risk patient populations.
Impact
The ACCURATE study has addressed a significant gap in care by diagnosing FH-positive patients in an acute cardiac care setting where genetic testing is not currently performed and therefore, these patients would likely remain undiagnosed. By providing treating physicians with genetic test results within 1 month of their patients’ ACS event, this study has raised awareness of the genetic basis underlying their patients’ premature cardiovascular events. While it is too early to measure changes in long-term outcomes, this approach ensures physicians are better informed to consider these insights in real-time clinical decision making and follow-up care. The rationale for conducting this research and the early results from ACCURATE has also inspired conversations with policy makers, industry experts, and healthcare providers in BC about the importance of integrating clinical FH genetic testing in the province.
Potential Influence
This study has the potential to change the standard of care for young patients with heart attacks by making FH genetic testing routine, especially for those with high LDL levels. This would lead to earlier detection of FH and may also highlight the importance of tailoring treatment intensity based on genetic findings, thus allowing physicians to identify those who may require more aggressive interventions to achieve lipid targets and prevent further cardiovascular events. Over time, this approach could help lower the rates of heart attacks and other cardiovascular events caused by undiagnosed or undertreated FH in British Columbia. Beyond its local impact, the study may provide a clear model for integrating genetic testing into acute cardiac care that can be adopted nationally and internationally.
Next Steps
ACCURATE is ongoing as patients in the Active Testing Phase are still being followed to assess outcomes including treatment intensification, lowest LDL-C achieved, guideline lipid target attainment at 15-months post ACS, and the rate of recurrent cardiovascular events. Next steps include assessing how these genetic results for FH impact physicians and their patients, particularly how they are integrated into clinical care. For this reason, we plan to conduct a survey to explore physicians’ reactions to and concerns regarding FH genetic results, assess the influence on clinical workflow, changes in treatment plans, and identify ways to support physicians in better diagnosing FH and delivering optimal care for patients. Additionally, exploring genetic testing for first-degree relatives may be a future direction to help identify more individuals with FH, therefore extending the reach and impact of the study.
Investigating psychomotor response to L-DOPA challenge as a biomarker for clinical outcomes in late-life depression: A pilot feasibility trial
Major depressive disorder (depression) is a common condition affecting older adults, also called late-life depression (LLD). Depression later in life can negatively impact overall health, including increasing the risk of developing dementia. With Canada’s aging population, it is important to develop more effective ways of managing this condition.
LLD is frequently associated with a phenomenon called psychomotor slowing, which is a decrease in the speed of both physical movements and information processing. The presence of psychomotor slowing can signify more severe illness and a risk of worse outcomes in LLD. Psychomotor slowing in LLD is related to the abnormal functioning of dopamine, a neurotransmitter that influences motivation, reward, and pleasure in the brain. This slowing may be reversible by taking a dopamine-like medication called levodopa (L-DOPA). However, we do not know whether there is a link between psychomotor slowing, reversibility by L-DOPA, and treatment outcomes in LLD.
I am a geriatric psychiatrist at St. Paul’s Hospital and a postdoctoral research fellow at the University of British Columbia. My study, which is supported by the CANTRAIN-CTTP & Michael Smith Health Research BC Post-Doctoral Studentship Award and conducted at St. Paul’s Hospital in Vancouver BC, will invite participants to receive two weeks of treatment with a drug called Levocarb which contains L-DOPA (an L-DOPA “challenge”). We will measure participants’ walking speed, overall speed of movements, and cognitive function before and after the challenge.
The goal of this study is to evaluate whether psychomotor slowing in LLD changes in response to changes in brain dopamine levels, and whether this change can predict improvements in depression symptoms and cognitive function following standardized antidepressant treatment. These data will improve our understanding of the biology of LLD and may enhance our ability to predict which treatments will be most helpful for older adults suffering from depression.
End of Award Update – February 2025
Results
My pilot clinical trial has provided some of the first-ever data on the psychiatric, psychomotor, and cognitive effects of levodopa (L-DOPA) in depressed older adults. So far, we are observing significant improvements in psychomotor speed, working memory, and depressive symptoms in response to a 2-week administration of L-DOPA.
Impact
This clinical trial has provided, to my knowledge, the first BC-based opportunity to participate in clinical interventional research for older adults living with depression. This research is providing access to a novel treatment approach which will benefit health outcomes for older adults in BC and, possibly in the future, the rest of Canada and beyond.
Potential Influence
This clinical trial is the first in a planned sequence of studies to investigate the usefulness of L-DOPA as a challenge medication to help predict response to other medications in late-life depression. If successful, this research will lead to a practical clinical tool that enables us to provide personalized, evidence-based treatment options for older adults with depression.
Next Steps
Early results from this study are being prepared for publication and will be presented at upcoming conferences. A follow-on study with a randomized component is currently being planned, which will build off our promising pilot data.