Autoantigen GAD-Vaccine is Safe for Children at High Risk for Developing Type 1 Diabetes
San Diego, California
June 12, 2017
Treatment with autoantigen specific therapies, such as Alum-GAD, is safe to give to children with an increased risk for developing type 1 diabetes, however, it does not prevent the development of the disease, investigators explained during a symposium presentation today on the research study, “A Double-blind, Randomized Investigator-initiated Study to Determine the Safety and the Effect of Diamyd® on the Progression to Type 1 Diabetes in Children With Multiple Islet Cell Autoantibodies,” at the American Diabetes Association’s 77th Scientific Sessions® at the San Diego Convention Center.
Glutamate decarboxylase, or glutamic acid decarboxylase (GAD), is an enzyme that is targeted by autoantibodies in people who later develop type 1 diabetes. Previous research reported that injections with GAD may preserve some insulin production for 30 months in people with type 1 diabetes; however, this had not been confirmed in larger scale studies. This double-blind, randomized, investigator-initiated study was conducted to determine the safety and the efficacy of alum-formulated GAD65 (Alum-GAD)¹ , on the progression to type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
DIAPREV-IT is the first prevention study where Alum-GAD was given before the onset of type 1 diabetes. The study aimed to test if it is safe to use Alum-GAD on children who are at high risk for developing the disease in an attempt to induce immune-tolerance earlier during the autoimmune process, and thereby prevent or delay the process leading to clinical type 1 diabetes. Known risk factors for type 1 diabetes include family history, genetics, geography and age, with the highest incidence of onset occurring in children between 4-7 years and 10-14 years.
The study was conducted from April 2009 to January 2017 in Sweden. The trial enrolled 50 children, aged 4-18 years, who did not yet have type 1 diabetes, and who had positive GAD-antibodies and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb or IAA). The children were assigned to receive either two injections of the previously tested dose of 20 µg Alum-GAD, administered as a prime-and-boost at days 1 and 30—as no serious adverse reactions have been observed with this regimen—or two injections of a placebo. Both intravenous (IvGTT) and oral glucose tolerance tests (OGTT) were performed before the first injection. Follow-up visits with the enrolled patients were conducted every three months for five years, with the OGTT repeated every six months and the IvGTT repeated at every full-year visit during the study. OGTT’s were also performed annually, and IvGTT and OGTT were alternatingly performed every six months
The results indicated that it is safe to administer Alum-GAD to children who are at high risk of developing type 1 diabetes; however, the trial did not find any significant effect on preventing type 1 diabetes in the small study sample. Since the group was composed of children with both normal and impaired glucose tolerance upon enrollment in the study, these subjects were known to progress to type 1 diabetes at different rates. Thus, it was not possible to perform specific analyses in subgroups of children. However, there was no difference in adverse events or serious adverse events between participants receiving the placebo or the active substance.
“Since our study shows that Alum-GAD treatment is safe, we want to further explore this treatment—either in different doses or in combination with other drugs—in future prevention studies that may impact patient care,” said chief investigator Helena Elding Larsson, MD, PhD, associate professor of pediatric endocrinology and diabetes at Lund University in Sweden. “For example, one option could be to use repeated increasing small doses as is common in classic immune tolerance treatment for allergic symptoms.”
“We collected a large number of immunological samples from the study that have yet to be analyzed to understand the possible mechanistic effects of Alum-GAD,” Larsson explained. “These results will be important to consider in developing new studies with combination therapies performed.”
To speak with Dr. Larsson, please contact the Association’s media relations team on-site at the San Diego Convention Center on June 9 - 13, by phone at 619-525-6250 or by email at email@example.com.
The American Diabetes Association’s 77th Scientific Sessions, to be held June 9-13, 2017, at the San Diego Convention Center, is the world’s largest scientific meeting focused on diabetes research, prevention and care. During the five-day meeting, health care professionals have exclusive access to more than 2,500 original research presentations, participate in provocative and engaging exchanges with leading diabetes experts, and can earn Continuing Medical Education (CME) or Continuing Education (CE) credits for educational sessions. The program is grouped into eight interest areas: Acute and Chronic Complications; Behavioral Medicine, Clinical Nutrition, Education and Exercise; Clinical Diabetes/Therapeutics; Epidemiology/Genetics; Immunology/Transplantation; Insulin Action/Molecular Metabolism; Integrated Physiology/Obesity; and Islet Biology/Insulin Secretion. Brenda Montgomery, RN, MSHS, CDE², President of Health Care and Education , will deliver her address on Saturday, June 10, and Alvin C. Powers, MD, President of Medicine and Science, will present his address on Sunday, June 11. Eight abstracts were selected by the Scientific Sessions Meeting Planning Committee to be presented on Tuesday, June 13, in the President’s Oral Session. These abstracts represent important research being conducted in the field of diabetes today. In total, the 2017 Scientific Sessions includes 378 abstracts in 49 oral sessions; 2,152 poster presentations including 50 moderated poster discussions; and 360 published-only abstracts.
About the American Diabetes Association
Nearly half of American adults have diabetes or prediabetes; more than 30 million adults and children have diabetes; and every 21 seconds, another individual is diagnosed with diabetes in the U.S. Founded in 1940, the American Diabetes Association (ADA) is the nation’s leading voluntary health organization whose mission is to prevent and cure diabetes, and to improve the lives of all people affected by diabetes. The ADA drives discovery by funding research to treat, manage and prevent all types of diabetes, as well as to search for cures; raises voice to the urgency of the diabetes epidemic; and works to safeguard policies and programs that protect people with diabetes. In addition, the ADA supports people living with diabetes, those at risk of developing diabetes, and the health care professionals who serve them through information and programs that can improve health outcomes and quality of life. For more information, please call the ADA at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn)
1 The brand product name for Alum-GAD is Diamyd®.
2 Disclosures for Brenda Montgomery. Employer: AstraZeneca Pharmaceuticals. Montgomery's role as President, Health Care & Education of the American Diabetes Association (Association) is a voluntary position to which she was elected by the members of the Association in 2015. She continues to recuse herself from any and all discussions, decisions or votes that have or could be perceived as having a conflict of interest with her employer.