Understanding Hypoglycemia and the CLEAR Study

The CLEAR Study is a groundbreaking, international research effort funded by the NIH that aims to help people with Type 1 diabetes (T1D) who can no longer sense when their blood sugar is dangerously low—a condition known as impaired awareness of hypoglycemia (IAH). Anna Casu, MD, Associate Investigator at the Translational Research Institute and Von Weller Family Chair in Type 1 Diabetes Research, answers our questions about this important study and why it matters.

Q&A with Dr. Anna Casu

What is hypoglycemia—and what is impaired awareness of hypoglycemia?
Dr. Casu: Hypoglycemia occurs when blood glucose levels drop below 70 mg/dL. In response, the body releases stress hormones that cause warning symptoms like tremors, palpitations, cold sweats, and shivering—prompting someone with T1D to eat and raise their glucose levels. However, about 1 in 4 people with T1D for 10 years or more lose the ability to feel these symptoms. This condition is called impaired awareness of hypoglycemia (IAH).

How does IAH impact people living with T1D?
Dr. Casu: People with IAH may not respond in time, or at all, to low glucose episodes, putting them at higher risk of severe hypoglycemia, including loss of consciousness.

What is the CLEAR Study, and why is it important?
Dr. Casu: The CLEAR Study is an NIH-funded trial led by top experts from around the world, including the TRI team. It’s testing innovative ways, using technology and behavioral interventions, to help people with T1D regain the ability to recognize low blood sugar. This study builds on over 30 years of research and could lead to better global standards for diagnosing and treating IAH.

What interventions are being tested?
Dr. Casu: The study will test various combinations of diabetes technology and educational programs designed to improve hypoglycemia awareness. Participants will be randomly assigned to different approaches.

What is the SMART design, and why is it used in this trial?
Dr. Casu: This study uses a SMART (Sequential Multiple Assignment Randomized Trial) design. If one intervention doesn’t work after a set period, participants are reassigned to another approach, making it more responsive and personalized.

What are the study’s primary goals?
Dr. Casu: The main goal is to improve hypoglycemia awareness. Researchers also hope to better understand who develops IAH, how to diagnose it early, and which treatments are most effective for different individuals.

How are participants monitored over the two-year period?
Dr. Casu: Participants will undergo regular evaluations to assess how well interventions are working.

Who is eligible to join the CLEAR Study?
Dr. Casu: Adults aged 18–75 who have had T1D for at least 10 years and have difficulty sensing when their blood sugar is low may qualify.

Why include both technology and behavioral interventions?
Dr. Casu: Smaller studies suggest that both methods can help restore awareness. This study will evaluate which option, or combination, is most effective, and for whom. IAH can severely limit independence and increase emotional strain for both patients and caregivers. Restoring awareness could dramatically improve quality of life.

What could this research mean for the future of diabetes care?
Dr. Casu: By advancing our understanding of IAH and how to reverse it, this research could help prevent it altogether, ultimately improving safety and daily life for people with T1D.

What would you say to someone hesitant to join a clinical trial like this?
Dr. Casu: Research is the only way to advance care. Participants benefit from expert support while helping future generations. As I often say: even the most brilliant scientific ideas are worthless if we can’t test them.