Type 1 diabetes (T1D) is the most common metabolic and autoimmune disease in children. Approximately 373,000 people in Germany have clinical type 1 diabetes and every year about 3,100 children and adolescents between the ages of 0 and 17 are diagnosed with the disease. In this chronic autoimmune disease, the immune system destroys the insulin-producing beta cells of the pancreas. Insulin helps regulate blood-sugar levels throughout the day and night, a key to managing diabetes. People with type 1 diabetes rely on insulin therapy (insulin injections) to help manage their blood-glucose levels. The food they eat, stress, illness, excitement and several other factors can all affect glucose levels, necessitating insulin therapy.
Protection for the beta cells
Scientists are searching to preserve beta cell function and delay or prevent the onset of clinical type 1 diabetes. "One option is to prevent the beta cells in the pancreas from dying," says Prof. Dr. Anette-Gabriele Ziegler. She is Director of the Institute of Diabetes Research (IDF) at the Helmholtz Center Munich, Head of the Diabetes Research Group at the Technical University Munich and a member of the German Center for Diabetes Research (DZD). In a joint study with Yale University New Haven, Ziegler et al were able to show that the destruction of beta cells by the body's own immune system can be reduced with the help of teplizumab*. In the randomized, placebo-controlled, double-blind Phase II study, a 14-day intravenous administration of teplizumab delayed the onset of clinical type 1 diabetes by an average of three years in people presymptomatic (stage 2) type 1 diabetes.
New study - PROTECT
In the new PROTECT clinical research study, researchers now intend to investigate whether the study drug teplizumab** can slow the loss of theremaining beta cells and preserve beta cell function in children and adolescents aged eight to 17 years with recently diagnosed type 1 diabetes.
DZD scientists from the University Hospital Carl Gustav Carus, the Paul Langerhans Institute Dresden, the Helmholtz Center Munich and the Medical Faculty of TU Dresden are also participating in the international study. A total of 300 children and adolescents at study centers in the USA, Canada and Europe are to be studied in the randomized, placebo-controlled double-blind Phase III trial. ***
Design of the study
Participants receive either the study drug or a placebo via intravenous infusion. Over a period of twelve days they are administered the respective infusion daily. The study consists of two courses. After six months the study participants therefore receive a daily infusion again for a period of twelve days. After 18 months the researchers will analyze the effects of the study drug based on beta cell function and other important measure of glycemic control including; long-term blood glucose value (HbA1c), blood glucose values and the required amount of insulin therapy.
"With this study we want to find out whether two courses of teplizumab in children and adolescents with newly diagnosed clinical type 1 diabetes can mitigate the destruction of beta cells and help to maintain insulin production for a longer period of time", explains Prof. Dr. Reinhard Berner, PI of the study and Director of the Clinic and Polyclinic for Pediatrics and Adolescent Medicine at Dresden University Hospital.
You can also obtain more information about the study on the Internet at https://theprotectstudy.com
* Background: Based on current knowledge, type 1 diabetes (T1D) is triggered by autoimmune reactions directed at the insulin-producing beta cells in the pancreas by specific white blood cells (T lymphocytes). The beta cell is destroyed and insulin production is reduced. Teplizumab binds to these T-lymphocytes and should thus prevent or reduce the destruction of the beta cells.
** The study drug teplizumab is a type of protein designed to modify the body's immune response in a manner that protects it from the damage caused by T1D. Teplizumab is referred to as a study drug as it has not been fully evaluated by the regulatory authorities and has as yet not been approved in any country. However, teplizumab has been investigated in numerous clinical trials, including children and adults with clinical T1D.
*** The effect of the study drug teplizumab is being investigated in the study. One part of the patients receives the study drug and the other part receives a placebo for control purposes. Neither the patient nor the physician knows which study participant receives which substance. Both groups are randomized, i.e. comparable in terms of severity of the disease, etc. The purpose of a Phase III study is to demonstrate and confirm the preliminary evidence gathered in the previous trials that the drug is, a safe, beneficial and effective treatment for the intended indication .
Kevan C. Herold, M.D., Brian N. Bundy, Ph.D., S. Alice Long, Ph.D., Jeffrey A. Bluestone, Ph.D., Linda A. DiMeglio, M.D., Matthew J. Dufort, Ph.D., Stephen E. Gitelman, M.D., Peter A. Gottlieb, M.D., Jeffrey P. Krischer, Ph.D., Peter S. Linsley, Ph.D., Jennifer B. Marks, M.D., Wayne Moore, M.D., Ph.D., Antoinette Moran, M.D., Henry Rodriguez, M.D., William E. Russell, M.D., Desmond Schatz, M.D., Jay S. Skyler, M.D., Eva Tsalikian, M.D., Diane K. Wherrett, M.D., Anette-Gabriele Ziegler, M.D., and Carla J. Greenbaum, M.D. for the Type 1 Diabetes TrialNet Study Group*for the Type 1 Diabetes TrialNet Study Group (2019). An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. NEJM