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.

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.

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.

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.

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.

Control of Line Complications with KiteLock (CLiCK) in the Critical Care Unit

Health Research BC is providing match funds for this project, which is funded by the CANTRAIN-CTTP & Michael Smith Health Research BC Doctoral Studentship 2023 Award Program.  

Supported through the CANHealth Network, MITACS Accelerate, the Royal Columbian Hospital Foundation, and SterileCare Inc., CLiCK is a pan-Canadian clinical trial that investigates whether locking Central Venous Access Devices (CVADs) with 4% EDTA fluid is effective in reducing CVAD-associated complications in adult critical care patients.  

Dr. Steven Reynolds, ICU Physician at Royal Columbian Hospital, Professor at Simon Fraser University, and Executive Lead at the Advancing Innovation in Medicine Institute, is the Senior Investigator of the trial, along site Drs. Anish Mitra, Gordon Wood, Daniel Ovakim, David Forrest, Mark James, Gloria Vazquez-Grande, and Wesley Jang as Site Principal Investigators. Marlena Ornowska is the Doctoral Student working on this project.  

A CVAD is a thin tube that is inserted into one of the large, central veins of a patient. This tube allows doctors and nurses to deliver medication, fluids, blood, or nutrients directly into the bloodstream. During breaks between medications or infusions, nurses fill the inside of the tube with salt water or citrate to keep it open and ready for the next use. This is called ‘locking’ the CVAD.  

Because a CVAD is a foreign object introduced into the body, patients may develop complications such as infection and blood clots. These may be prevented by using a locking fluid has anti-bacterial and anti-thrombotic properties. One example of this type of fluid is called 4% EDTA. Our trial is investigating whether patients whose CVADs are ‘locked’ with 4% EDTA experience fewer complications than those who have their CVADs locked with salt water or citrate. This project will help us understand and create safer CVAD care in this vulnerable patient population.  

Effects of Cannabis on Stress Response: A Double-Blind Randomized Placebo-Controlled Crossover Trial (NCT05261321)

Approximately 50% of Canadians have used cannabis at least once in their lifetime. The vast majority of cannabis users report using cannabis to reduce stress. While there is some evidence to suggest that cannabis may impact the body’s stress regulation systems via the endocannabinoid system, there remains limited experimental evidence that cannabis does indeed reduce acute stress and the effects of cannabis on the brain during acute stress are not well understood. The current randomized control trial aims to examine the effects of oral cannabis (THC and THC+CBD vs placebo) on acute stress response in humans using a combination of functional Magnetic Resonance Imaging, psychoneuroimmunological assays, and subjective assessments. With stress dysregulation being a major risk factor for a range of physical and mental health disorders, and with stress reduction being a primary reason for cannabis use, the effects of cannabis on stress regulation may have significant public health implications.  

This study is occurring at the University of British Columbia. The study team includes Karina Thiessen (awardee), study qualified investigator Dr. Christian Schütz and co-investigators Dr. Alasdair Barr, Dr. Clare Beasley, and Reza Rafizadeh. Funding support includes research grant and student stipend funding from the Canadian Centre on Substance Use and Addiction, BC Mental Health and Substance Use Services, Brain Canada, and the Michael Smith Health Research BC-CIHR CANTRAIN Clinical Trials Training Platform Doctoral Studentship. 

Cyclic Progesterone and Spironolactone Treatment for Polycystic Ovarian Syndrome (PCOS)

Individuals living with androgenic-PCOS have had few choices and effective therapy options for many years. This 6-month open-label trial is exploring cyclic oral micronized progesterone and spironolactone as an option for individuals who are not tolerating or are dissatisfied with CHC. There is a strong rationale for use of each of these therapies. It may be that these results lead to improved PCOS quality of life, more regular cycles, less psychologically devastating skin/hair changes and improved fertility. Should this pilot study show what we expect—better PCOS-Q quality of life including emotional, weight, hirsutism, cycles and fertility domains, it will have provided the first evidence supporting a potentially important new therapy for PCOS. This new therapy might be life-changing for some individuals in BC who are now struggling to deal with the changes associated with living with androgenic-PCOS. This project is supported by CANTRAIN-CTTP & Michael Smith Health Research BC Masters’ Studentship 2023 Award Program. Dr. Jerilynn C. Prior, the principal investigator is an endocrinology professor at the University of British Columbia, is the scientific director of the Centre for Menstrual Cycle and Ovulation Research and my supervisor. 

Effects of budesonide on responses to diesel exhaust and allergen exposures in allergic rhinitis

About one in every four Canadians suffers from a disease called allergic rhinitis. This causes symptoms like sneezing, itching, watery eyes, and difficulty breathing, especially when people inhale allergens from sources like trees and grasses. A type of medicine called nasal corticosteroids can usually help reduce these symptoms.
However, we do not know how exposure to air pollution, such as diesel exhaust, which is common in cities and industrial areas, might make this disease worse. We also do not know if nasal corticosteroids can help reduce the effects of exposure to diesel exhaust.
To investigate this, we conducted a study where we exposed people with allergic rhinitis to allergens and diesel exhaust separately, both with and without the use of nasal corticosteroids. This study was conducted at the Air Pollution Exposure Laboratory (APEL), a leading research facility that uses advanced controlled exposure methods to study how air pollution affects human health.
I will be looking at changes in how the nose functions as well as the levels of cells and small proteins in the nose that can underly symptoms, to see if nasal corticosteroids can effectively treat the effects of exposure to allergens and diesel exhaust.
The Master’s Studentship 2023 Award, supported by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) Clinical Trials Training Program and Michael Smith Health Research BC, will thus help us evaluate a low-cost, accessible treatment for this growing health concern. This work will be supported by the Legacy for Airway Health (LAH), which supports knowledge translation and allows us to consult directly with patients. Since this work is being done in British Columbia, it also helps build local expertise in respiratory clinical trials and research.