Category: Clinical Trials

Clinical Trials

In addition to funding critical type 1 diabetes (T1D) clinical trials, a key focus for JDRF is increasing awareness of and participation in trials. All new interventions, from drugs to devices to programs like mental health and peer support, must undergo clinical trials before they can be applied in everyday practice and benefit the people who need them most. By facilitating progress in clinical trials, JDRF is helping to ensure that the most promising T1D research advances can make a difference for anyone affected by the disease. asdfsdf

We know that many clinical trials fail due to low participation — simply because potential participants didn’t know about them. Over 80% of JDRF-funded trials are delayed due to low participation. There can be many reasons for this, lack of information about what’s involved in a clinical trial, or concerns about risks. Below are answers to some key questions we hear from our community – as well as some of the important benefits that many research participants experience. 

What is a clinical trial:

Almost any new test, treatment, device, or program that will become part of clinical practice, must first undergo clinical trials.  This can include drugs (such as types of insulin), devices (such as insulin pumps), virtual care platforms (such as digital health apps), behavioural therapy (such as peer support), education programs (such as diabetes awareness programs), exercise and diet programs (such as high intensity exercise regimens), and many more. The purpose of clinical trials is to determine the safety (including possible side effects) and efficacy (how well the intervention produces the expected response) of the intervention.  

This is a general overview of clinical trial phases for development of a new drug:  

What is it like to participate in a clinical trial?

Participating in a clinical trial can be a daunting prospect for many people. It involves undergoing a new treatment or therapy that has not yet been fully tested for T1D, which can understandably cause fear and uncertainty. Additionally, there may be logistical, financial, or personal barriers that prevent individuals from participating in clinical trials. However, these factors vary widely across trials, as some are minimally invasive (e.g., signing up for a registry), entirely virtual (e.g., a mental health app), or even look at improving upon a known beneficial intervention (e.g., a new physical activity regimen). Trials can vary from virtual involvement of only a few hours, to surgical procedures with year(s) of follow-up, and everything in between.

One of the most significant fears someone may have about participating in clinical trials is the fear of the unknown. Many people are nervous about trying a new treatment or therapy that has not yet been fully tested. They may worry about potential side effects or long-term risks of the treatment. Or that the treatment may adversely impact their current T1D management. However, it is essential to remember that clinical trials are designed to be as safe as possible, and all interventions undergo rigorous ethical approval and, for drugs and devices, Health Canada approval before being offered to participants. 

Another fear individuals may have about participating in clinical trials is the fear of losing control over their healthcare decisions. They may worry that they will not be able to make their own decisions about their care or that they will be pressured into participating in a trial. However, all clinical trials are voluntary, and individuals can choose to withdraw from a trial at any time if they are not comfortable. 

Logistical barriers can also prevent individuals from participating in clinical trials. For example, clinical trials may take place in a different city or province, which can make it challenging for some to attend appointments. Additionally, some trials may require participants to take time off work or arrange childcare, which can be difficult for some people. However, many trials have a travel budget to bring participants in from other cities or provinces at no cost to the participant, and research teams tend to make efforts to work around participants’ schedules, where possible. 

Finally, concerns about financial barriers can prevent individuals from pursuing participation in clinical trials. However, many clinical trials offer compensation for participants, which can cover, or offset costs related to travel or taking time away from work, school, or childcare. Potential participants are informed about this upfront before agreeing to participate in the trial. 

What is a placebo?

Many people are concerned that they will be in the placebo group of a clinical trial and will invest time and energy to not receive any benefits. While this is a very valid concern, there are still major benefits to being in a placebo group: 

  1. All participation is valuable: even being in a placebo group helps contribute to a cure or advancement in T1D research and resources. 
  2. Added care: participants in placebo groups still benefit from the added healthcare that is standard in a clinical trial. This may be especially beneficial for people with T1D who don’t have routine access to endocrinologists / medical teams for any reason (such as living in a more rural area).  
  3. Compensation/access: if trials have a budget to compensate participants for their involvement, everyone will be compensated equally, regardless of group (placebo vs. intervention) assignment. In addition, if the intervention is successful, participants in the placebo group may have first access to it following the trial. 

There are different ‘types’ of placebos for clinical trials; not all placebo groups receive a ‘sugar pill’: 

  1. Intervention vs Nothing (sugar pill): this is used when the intervention is new enough that there isn’t any existing therapy to compare it to. For example, in clinical trials of teplizumab, the drug was compared to a ‘sugar pill’ since no other disease-modifying therapy existed to compare it to. 
  2. Intervention vs Standard of Care: this is used when there is an existing, similar therapy available. The new intervention will be compared to the existing standard of care to determine if its efficacy is equal to, or better than, what already exists. For example, new insulin pumps or CGMs may be compared to existing models, or a new type of insulin may be compared to an insulin already on the market.  
  3. Crossover Design: this design is frequently used for devices, behavioural, exercise, education, or mental health interventions. One group will receive the intervention for a period of time, while the ‘placebo group’ is placed on a waitlist and monitored/surveyed without any intervention. After a set time, the groups will switch and the ‘placebo group’ will receive the intervention while the first group is followed for a period of time without the intervention. Everyone in the study receives the intervention, and researchers get an extended period of tracking the efficacy of the intervention.  

What is informed consent? 

All clinical trials start with an informed consent document.  This document will outline everything about the research, including all the procedures, visits, potential side effects, supports in place, etc. It is the responsibility of the research team to walk you through this document and answer any questions that you may have.   

This document will also indicate the ethical approval steps that the study has undergone (typically through a university or hospital research ethics board). Information will also be given as to how you can report any adverse side effects, how you can leave the study at any time, and how you can contact the research ethics board if you have any concerns.  

It’s important to note that consent to participate in research must be free, informed, and ongoing. This means that consent is given voluntarily, that the potential participant fully understands the purpose of the research, their involvement, the risks, and benefits, and that consent is ongoing from the beginning to the end of the study. Please note that an informed consent document is not a legally binding document, and participants can withdraw from a study at any point in time without penalty. 

What is an observational clinical trial?

Clinical trials do not always require an intervention being given to the participant. There are also observational research trials where the research team is recording something from the participant without giving them anything. Examples of this may be T1D screening (such as TrialNet, where the research team is taking and testing blood samples to determine risk of T1D), follow up studies from previous trials (such as teplizumab follow-ups which are tracking the initial participant group for a number of years), or disease registries (such as BETTER, where the research team is recording information about Canadians who live with T1D so that all researchers in Canada can have a better understanding of the T1D population).

If you are interested in participating in research but don’t know if you are prepared to receive an intervention, please consider taking part in an observational trial such as the BETTER registry. This is open to all Canadians with T1D (persons 14 and over sign up for themselves, parents/caregivers sign up on behalf of persons 13 and younger with T1D).  

Where can I find out more information about T1D trials? 

How else can I get involved?

To help ensure that JDRF’s Clinical Trials Education Program is aligned with the needs of the T1D community, we will grow and engage an existing group of volunteers with lived experience of T1D who advise on our research programs. Through the Clinical Trials Education Program, these Research Collaboration Volunteers will have the opportunity to share their diverse experiences and perspectives with research teams to influence the design and execution of clinical trials and other research studies.

Although not essential, we are particularly interested in engaging people with lived experience of T1D (either as a researcher in any field, a past participant in research studies, or any other significant exposure to research).

This crucial group of volunteers will promote diversity in T1D research, ensure that the participant voice consistently informs research, and help to accelerate the translation of knowledge between researchers, the T1D community and other stakeholders.

Please email research@JDRF.ca to learn more or express your interest.

Support JDRF’s Clinical Trials Education Program: please email jbavli@jdrf.ca 

Participating in clinical trials may change the course of type one diabetes

January 23, 2022 is the 100th anniversary of the first successful insulin injection for diabetes in a human.  Prior to this, a diagnosis of type 1 diabetes (T1D) meant certain death. On this date, a fourteen-year-old boy named Leonard Thomspon, who was dying from complications of T1D received the first real treatment for the disease. He would live another 13 years. Leonard could be considered the first human in an insulin clinical trial. As a result, millions across the globe can now better manage their diabetes.

This day has special meaning to our family. Our daughter Tilla was just 10 years old when she was diagnosed with T1D in the summer of 2019. Now, like everyone who lives with this disease, her days are a series of decisions, tracking her blood sugar and insulin levels, and measuring her food, particularly carbs. And although we are fortunate to have the best diabetes technology available to us, it can still be immensely stressful at times. It is a 24-7 disease with no days off.

After Tilla’s diagnosis, we started researching available clinical trials that she could be enrolled in, and Tilla bravely rose to the challenge. She enrolled in the PROTECT study, which is testing an investigational medicine called teplizumab – a drug JDRF Canada has supported earlier trials of. It is hoped teplizumab will help people with T1D to continue making more of their own insulin and reduce or even eliminate the need for insulin injections for many months.

PROTECT is a randomized controlled trial involving a placebo group. Despite knowing that Tilla could be placed in the placebo group, we still chose to participate, with the hopes that not only could it change the disease course for Tilla in the short term, but in the future could impact thousands of other people like her who are diagnosed with T1D every year.

Our son Allan is also enrolled in a T1D clinical trial at Sick Kids hospital in Toronto, ON. He has all the antibodies for the disease, which puts him at far greater risk of developing it in the future. Along with his mother, Allan has flown to Toronto twice. He takes one pill per day/ two pills per day on weekends. It is our hope that if he is not receiving the placebo – this treatment might prevent or delay him from developing T1D. And even if it does not, we know that he is still contributing to advancing scientific knowledge of how we might better screen for and prevent diagnoses of T1D.

Being involved in clinical research makes us feel as a family that we are directly and personally contributing to helping find a cure for this devastating disease. And we believe this is an important message. Participation in clinical trials is the only way we can get treatments to market and to everyone who can benefit from them. We consider anyone enrolled in clinical trials heroes.

What many people do not know is that the first insulin injection took place on January 11, 1922, but Leonard Thompson had an allergic reaction to it. And that when that first injection did not work, he took another step forward and tried again. From the bravery of one teenage boy, came millions of people whose lives have been saved by insulin. And every year across the globe, people living with T1D celebrate their ‘insulin anniversary’ while waiting for the next breakthrough in diabetes.

Every person who participates in a T1D clinical trial study helps us get closer to a cure. We recognize their courage and are so grateful for their help in accelerating research that will one day mean a world free from diabetes.

We are grateful to JDRF Canada, whose primary goal is funding the most promising research that will move us beyond insulin and toward a cure for T1D. Their investment in this research means that we can participate in these important clinical trials.

Henrik Karlsson, Anna, Tilla and Allan Karlberg, on behalf of JDRF Canada

www.jdrf.ca

Vancouver, BC

Exciting update in Sernova’s type 1 diabetes (T1D) trial

Principal researcher confirms trial participants with a history of hypoglycemia unawareness are now insulin independent.

Funding cell replacement therapies research is one of JDRF’s most critical undertakings globally, in its efforts to support the most promising cure-based research into type 1 diabetes (T1D).  

On January 10, 2022, Sernova Corp. provided a progress update on its Phase 1/2 T1D clinical trial, a JDRF-funded clinical trial of its cell replacement therapy. The findings were presented by Dr. Piotr Witkowski, the clinical trial’s Principal Investigator at the University of Chicago.

Sernova is a clinical-stage regenerative medicine company and has continued to demonstrate promising results for its Cell Pouch System™. When transplanted with insulin-producing islets, this system has consistently demonstrated in ongoing trials that it can produce insulin in people T1D, and participants maintain more consistent blood sugar levels. Additionally, it has demonstrated ongoing safety and tolerability of the system. In Sernova’s current clinical trial, patients must take immunosuppressive drugs to prevent rejection of the implanted cells.

Sernova’s approach for T1D involves transplanting purified islet cells (the cells in the pancreas that produce insulin and that are destroyed in people with T1D) from organ donors into the Cell Pouch™, an implantable medical device that allows these cells to survive long term and produce insulin. This is a cell replacement therapy that has the potential to be a T1D cure.

The objective of Sernova’s Phase 1/2 clinical trial is to assess the safety, tolerability and efficacy the Cell Pouch™ transplanted with insulin-producing islets in trial participants with T1D who have a history of hypoglycemia unawareness and severe hypoglycemic events.

To be in the study, participants must meet stringent eligibility criteria including, but not limited to, long-standing T1D, recent episodes of hypoglycemic unawareness and an absence of glucose-stimulated C-peptide detectable in their bloodstream (a biomarker that demonstrates the body is making its own insulin).

Hypoglycemia unawareness is a person’s inability to recognize the symptoms of low blood sugar before they become severe or even fatal. It typically occurs when blood glucose levels are below 3.0 mmol/L and is estimated to affect approximately 15% of people with T1D.

Highlights from the study include:

  • Maintained and ongoing safety and tolerability of the Cell Pouch™
  • Islet transplantation to the Cell Pouch™ resulted in the establishment of new, measurable islet function, documented by detectable levels of stimulated C-peptide in the first three participants who completed the course of transplants.
  • A supplemental, single intraportal islet transplant was enough for the first two participants to achieve and maintain sustained ongoing insulin independence and freedom from severe hypoglycemic events for over 21 and 2 months, respectively.
  • The third transplanted participant who recently completed their course of Cell Pouch™ transplants and a supplemental intraportal islet infusion, saw improvements in glucose control, near-normal levels of C-peptide, an absence of severe hypoglycemic events and reductions in daily insulin use.
  • Three additional participants are progressing through the study.

Sernova’s Cell Pouch™ System was created with the goal of one day treating people with T1D and other chronic diseases using stem cell-derived technologies, that will not require immunosuppression. Sernova is partnering with other companies to advance the Cell Pouch™ system to testing using a stem cell-derived source, as well as approaches that will reduce or eliminate the need for immunosuppression.

To date, between our partner organizations JDRF has invested more than $140 million USD in cell-replacement therapy research for T1D. As we celebrate the 100th anniversary in 2022 of the first successful insulin injection, this is another example of Canadian excellence in diabetes research that is accelerating us towards cures.

Celebrating Leonard Thompson Day

January 23rd marks the 100th Anniversary of the first successful insulin injection

JDRF’s primary goal is to cure type 1 diabetes (T1D) through research – as quickly as possible. To support people with T1D while cure research is advancing, we also fund ground-breaking research that seeks to make life with T1D easier, safer and healthier. With the discovery of insulin 100 years ago, JDRF is committed to funding the most promising research to move us beyond this treatment and toward cures.

1921

Before insulin treatment, a diagnosis of type 1 diabetes meant inevitable death. T1D destroys the beta cells in the pancreas that make insulin, without which, the body cannot maintain healthy blood sugar levels.

In 1921, Frederick Banting and Charles Best discovered that the pancreas produced the insulin hormone under the directorship of John Macleod at the University of Toronto. With the help of James Collip, they purified a synthetic version of insulin and produced the first real treatment for diabetes. To this day, it remains one of the most important scientific breakthroughs in the medical field, often called ‘Canada’s gift to the world’.

January 11, 1922

On this date, fourteen-year-old Leonard Thompson, a teenage boy who was dying from T1D complications, became the first person to receive an insulin injection. But instead of lowering his blood sugar, it caused an allergic reaction. Leonard’s doctors went back to the lab, where they worked nearly around the clock to improve the formulation. 

January 23, 1922

Almost two weeks later, they returned to Leonard’s bed with a new syringe of insulin. With this version, Leonard’s symptoms began to disappear, and he regained his health. He would live another 13 years. The discovery of insulin, along with Leonard’s willingness to try this new treatment meant the death sentence that was T1D could be lifted, and people around the world could use insulin to manage their diabetes.

The importance of clinical trials

Research is how insulin was discovered and it is how we will find the next generation of therapies for T1D, and eventually a cure.

And clinical trials are an essential component of medical research and development. While Leonard’s receiving the first insulin to human injection was not known as a “clinical trial,” at the time, his participation allowed his doctors to rework and refine the formula that would make it a successful treatment for diabetes for over 100 years. In modern terms, Leonard was the first human participant in a clinical trial to test the impact of insulin on T1D.

This demonstrates the far-reaching impact of clinical trials. These studies can help bring new, better treatments to market that will impact the lives of millions. Thanks to Leonard Thompson, the updated version of insulin became a true breakthrough in diabetes care.

Funding cell replacement therapies research is one of JDRF’s most critical undertakings globally, and between our partner organizations we have invested more $140 million USD to date.

JDRF funds stem cell derived beta cell replacement trials that are ongoing right now, like those at ViaCyte, Vertex and Sernova and from here we may witness the research that leads to a T1D cure.

Participating in clinical trials

JDRF is funding many clinical trials, and one of the biggest challenges is finding volunteers to take part in studies – and it’s often because they simply didn’t know they could. It is also important to have a diverse group of participants who represent the Canadian T1D community, so that potential therapies and treatments can be tested for efficacy against the larger group who will be using them. When someone participates in a clinical trial, they help all people living with T1D, by enabling research towards better health outcomes and cures.

Choosing to participate in a clinical trial is a very personal decision. Early access to promising new treatment can be an enormous benefit. Others have found that by participating in a clinical trial, they learned more about their health or T1D management. And it can be motivating to know you are contributing to helping accelerate research that can improve the lives of people living not only with T1D, but other chronic conditions as well.

To learn more about Canadian clinical trials, and to find studies near you: https://jdrf.ca/research/clinical-trials/

One person can make a difference – watch Tilla’s story of participating in clinical trials after her T1D diagnosis

On January 11, 1922, Leonard Thompson took a leap of faith. And when that first injection did not work, he took another step forward and tried again. From the bravery of one teenage boy, came millions of people whose lives have been saved by insulin. And every year across the globe, people living with T1D celebrate their ‘insulin anniversary’ while waiting for the breakthrough that will move us beyond insulin and towards a cure.

Every person who participates in a T1D clinical trial study helps us get closer to moving therapies from the lab to the market. We recognize too their courage and are so grateful for their help in accelerating the research that will one day mean a world free from diabetes.

JDRF-funded clinical trial of adjunct-to-insulin therapy seeks T1D teen participants

Adolescence can be a challenging time to manage type 1 diabetes (T1D). Life (and hormones!) change in all sorts of ways, and many teenagers experience higher than recommended blood glucose levels as a result, which can mean an increased risk of complications later in life. The study of novel therapies that can improve glycemic control in teens with T1D and reduce the risk of diabetes complications and is critical to improving the lives of youth living with diabetes.

Adjunct-to-insulin therapy – ie, taking another drug alongside usual insulin treatment – is one approach that could help on both fronts. For example, SGLT2 inhibitors are a class of oral medications approved for type 2 diabetes that stop glucose from the blood from being absorbed by the kidneys, instead encouraging glucose to be released in urine. Dr. Farid Mahmud and his team at the Hospital for Sick Children in Toronto are now recruiting for a JDRF-funded clinical trial that will test the safety and efficacy of an SGLT2 inhibitor called dapagliflozin in teens with T1D.

The research team is seeking participants aged 12-18 years with established type 1 diabetes in the Greater Toronto Area (Hospital for Sick Children) and Southwestern Ontario (Children’s Hospital of Western Ontario, London) who may be eligible to participate in the Adolescent Type 1 Diabetes Treatment with SGLT2i for Hyperglycemia & Hyperfiltration trial – also known as ATTEMPT attempt.study@sickkids.ca.

SGLT2 inhibitors such as dapagliflozin can improve blood sugars, increase time in range and decrease kidney pressure, called hyperfiltration. Studies in adults with T1D have shown that SGLT2 inhibitors can lower HbA1c, insulin dose and weight. By alleviating glucose absorption in the kidneys, these drugs can also help prevent long term damage to these organs.

What is the ATTEMPT study?

ATTEMPT is a 22-week clinical trial that aims to determine the safety and effectiveness an SGLT2 inhibitor called dapagliflozin on managing blood glucose and on improving kidney function in adolescents aged 12 to 18 with T1D. The study is being conducted to determine how this therapy can benefit and be used effectively in adolescents with T1D.

ATTEMPT is led by Dr. Farid Mahmud, an endocrinologist and researcher at The Hospital for Sick Children in Toronto. Dr. Mahmud’s overall research focus is diabetes, clinical and translational research relating to other autoimmune conditions (such as celiac disease), and early evaluation and prevention of diabetes-related complications. His research interests include the evaluation of medication and lifestyle interventions in high-risk pediatric groups and the evaluation of impact of the social determinants of health in youth with diabetes. He is also actively engaged in patient-centered research as part of the CIHR Strategies for Patient Oriented Research (SPOR- Can-SOLVE CKD) and as part of the JDRF-funded AdDIT (Adolescent Diabetes Cardio-renal Intervention Trial). 

What does joining the ATTEMPT study entail?

Once enrolled in the study, a participant can expect:

  • 5 in-person visits over 22 weeks
  • A random assignment to the dapagliflozin group, or the placebo group (a small pill that contains no active medicine)

While part of the study, participants will:

  • Keep taking insulin
  • Wear a continuous glucose monitor (CGM)
  • Test for blood ketones
  • Report any adverse events

Study participants will be compensated and provided support for costs associated with travel or parking. To learn more about the study and how to enroll, please contact: 416-813-7654 ext. 204517 or email  attempt.study@sickkids.ca