A 10-year study of a treatment to delay the development of Type 1 diabetes in individuals at high risk did not meet the study goals of delaying progression from normal glucose tolerance to abnormal glucose tolerance or clinical diagnosis, although the study drug, abatacept, impacted immune response and preserved insulin production during the one-year treatment period.
Findings from the TrialNet Abatacept Prevention Study, which will inform future research by providing important new information about how abatacept impacts Type 1 diabetes progression, were published online by Diabetes Care.
The group treated with abatacept, which changes the way immune cells communicate, maintained beta cell function better than the placebo group at 12 months, according to TrialNet Abatacept study chair Bill Russell, MD, director of the Division of Pediatric Endocrinology and Diabetes at Vanderbilt University Medical Center.
But improved beta cell function was not sustained 12 months after treatment ended, he said.
“Every study gives us critical information that moves us one step closer to our ultimate goal: a future without Type 1 diabetes,” Russell said. “This study helped us learn more about how abatacept works and its impact on disease progression.”
The Abatacept Prevention Study opened in 2013 and enrolled 212 participants between the ages of 6 and 45 who were at increased risk for Type 1 diabetes.
All participants had two or more diabetes-related autoantibodies and normal glucose tolerance, defined as stage 1 of Type 1 diabetes. Risk was identified by TrialNet screening, which detects the autoantibodies that signal the disease in its earliest stages, often years before symptoms appear.
In the treatment phase of the study, participants received 14 intravenous infusions over one year — three in the first month, then monthly for 11 months. Assigned randomly by computer, half of the participants got the study drug and the other half received a placebo infusion that looks the same as the study drug but is inactive.
Neither researchers nor participants knew who was in which group until the end of the study. After the first year, participants visited a TrialNet site twice a year for monitoring until the study ended.
In an earlier TrialNet study for people newly diagnosed with clinical Type 1 diabetes (now defined as stage 3), participants were treated with abatacept for two years. At the end of two years, those treated with abatacept had 59% better insulin production and a 9.6-month average delay in progression of insulin loss compared to those who received the placebo. That difference extended out to three years.
“Comparing findings from both studies provides important new information and direction for future research,” Russell said. “By studying abatacept in both stage 1 and stage 3 we have opened the door to additional research asking if continued treatment would preserve the transient beneficial effect of abatacept on beta cell function or if starting abatacept in stage 2 might more effective. We also want to know if combining abatacept with another therapy could prolong its impact.”
TrialNet is currently planning a new study to test abatacept in combination with rituximab, another drug that targets the immune system, in people newly diagnosed with Type 1 diabetes.
Expected to open for enrollment later this year, the study will be the first to test these two drugs consecutively (one after the other). Separate TrialNet studies showed each drug individually helped preserve insulin production in people newly diagnosed with Type 1 diabetes. By combining the two therapies, researchers expect more individuals to maintain insulin production during and possibly after treatment.
TrialNet, the largest clinical trial network assembled to change the course of Type 1 diabetes, is funded by the National Institutes of Health (NIH) through grant number (NCT00097292.
For more information the abatacept prevention study or about screening for Type 1 diabetes risk if it runs in your family, contact info@trialnet.org, visit www.trialnet.org, or contact the Vanderbilt Type 1 Diabetes TrialNet Program at (615) 936-8638.
