Pediatricians Eric Felner, MD, MSCR, and Mark Rigby, MD, PhD, have launched a phase II multi-center clinical trial evaluating whether intramuscular injections of alefacept (AmeviveÂ®) halt or slow the destruction of insulin-producing beta cells in the pancreas of patients recently diagnosed with Type 1 diabetes. Rigby is the trialâ€™s national program director and both serve as the co-lead investigators at the Emory and Children’s Healthcare of Atlanta site.
The clinical study, the Research Trial of Inducing Remission in New-Onset Type 1 Diabetes with Alefacept (T1DAL), will test the ability of alefacept to reduce the activity of T cells and protect the residual beta cells in individuals newly diagnosed with Type 1 diabetes from ongoing autoimmune destruction.
â€œThis project brings together key basic and clinical discoveries in many fields inside and outside Type 1 diabetes research, over many decades,â€ says Rigby, an assistant professor of pediatrics and surgery in the Emory University School of Medicine and a physician at Childrenâ€™s Healthcare of Atlanta.
Once called juvenile diabetes, Type 1 diabetes does not just occur in children. It refers to a form of diabetes mellitus that is the result of an autoimmune disorder. In those with diabetes, T cells destroy the beta cells, the insulin-producing cells residing in the pancreas. Insulin is needed to maintain normal levels of blood glucose, which in turn, allows cells to function normally. When Type 1 diabetes is initially diagnosed, it is believed that a substantial number of beta cells in the pancreas are still viable and continue to produce a small amount of insulin, but production lessens over time.
Although alefacept has never been tested in patients with diabetes, it has already been approved by the FDA for use in treating plaque psoriasis. Both Type 1 diabetes and psoriasis are chronic autoimmune diseases involving T cells, which normally protect the body from infections. T cells are exquisitely important for protective immunity against viruses and bacteria. In fact, if a personâ€™s T cell count falls, he or she is susceptible to opportunistic infections. However, in Type 1 diabetes and psoriasis, overactive or renegade T cells end up damaging other cells. In the case of psoriasis, T cells attack the skin, causing lesions and scaling.
â€œIn T1DAL, we are targeting what we believe to be the most damaging, rogue immune cells in the body that are actively involved in the destruction of beta cells early on in Type 1 diabetes,â€ says Rigby. â€œDue to alefaceptâ€™s use in the treatment of another immune-based disease and the safety profile established with that illness, we are confident the drug will have minimal impact on the protective aspects of the immune system. We believe that this study is one critical step in the path to finding a cure for this disease.â€
Felner himself was diagnosed with Type 1 diabetes in 1978 at Egleston Childrenâ€™s Hospital. He is now an associate professor of pediatrics in the Emory University School of Medicine and a physician at Childrenâ€™s Healthcare of Atlanta. Since his diagnosis he has managed to control the diabetes with insulin therapy, including use of a continuous insulin pump for the past 11 years. Despite this, he says his diabetes is still not cured.
â€œI have been caring for children with Type 1 diabetes for almost 15 years and these studies are finally providing hope of finding a cure,â€ says Felner.
The T1DAL trial is seeking 66 eligible participants at approximately 15 clinical research centers nationwide including Emory and Childrenâ€™s Healthcare of Atlanta. Participants must be between the ages of 12 to 35 years and must have been diagnosed with Type 1 diabetes mellitus within 100 days of enrollment in the trial. Enrollment is expected to continue for approximately two years.
Eligible participants will be randomly assigned to receive weekly intramuscular injections of alefacept or a placebo for two 12-week periods.
According to Rigby, at least 80 to 90 percent of people who develop Type 1 diabetes are children. â€œWe know that there are up to two million people in North America who have Type 1 diabetes. About 30,000 people a year develop it. And just in Atlanta, there are probably 400 children who will develop the disease every year. Every day thereâ€™s another child diagnosed–thatâ€™s another way to think about it.â€
The T1DAL trial is being conducted by the Immune Tolerance Network (ITN) and is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Additional funding for the study is provided by the Special Statutory Funding Program for Type 1 Diabetes Research, a special appropriation for research on the prevention and cure of Type 1 diabetes. Astellas Pharma US Inc. is providing the AmeviveÂ® for the study.
In addition to the current study, Rigby and Felner have been leading two others. The first trial, START, involves ThymoglobulinÂ®, a mixture of antibodies that attaches itself to T cells, temporarily eliminating a large proportion of them from the bloodstream, with the hope that new T cells that replace the old T cells will learn to accept the beta cells rather than attacking them. This trial officially closed on March 31, 2011, but follow-up for these patients will continue for two years after they enrolled.
The second study, RETAIN, is a two-part trial investigating the effect of intravenous Alpha-1 antitrypsin (AAT, Aralast NP) on preserving beta cell function and whether AAT will help slow the progression of Type 1 diabetes. This trial is still recruiting.
More information about the T1DAL trial and participating clinical research centers can be found at www.t1dal.org or http://www.clinicaltrials.gov/ct2/show/study/NCT00965458. Or you may e-mail Type1diabetes@emory.edu or call 404-785-T1DM (8136) to contact Emory directly.
The trials are part of the Clinical and Translational Research Center â€“ one of 14 priority centers in the Emory-Childrenâ€™s Pediatric Research Center led by Emory University and Childrenâ€™s Healthcare of Atlanta. The Clinical and Translational Research Center is currently recruiting new faculty and staff.
The other centers include hematology and oncology; immunology and vaccines; transplant immunology and immune therapeutics; pediatric healthcare technology innovation; cystic fibrosis; developmental lung biology; endothelial biology; cardiovascular biology; drug discovery; autism; neurosciences; nanomedicine; and outcomes research and public health.