January 9, 2009

Trial seeks to save insulin-producing cells

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Daniel Albright is taking part in a novel study at the Vanderbilt Eskind Pediatric Diabetes Clinic. (photo by Dana Johnson)

Trial seeks to save insulin-producing cells

Daniel Albright skipped school on Nov. 24 in order to fight a battle, one being waged inside the 16-year-old's own body.

Albright is one of four local participants enrolled in a first-of-its-kind medication study at the Vanderbilt Eskind Pediatric Diabetes Clinic. It is part of the national Type 1 Diabetes TrialNet series of studies, this one testing an arthritis drug called Abatacept to see if it can stop a rogue immune system from killing the body's precious insulin-producing cells.

Albright and the other participants will repeat an intensive clinic visit every two weeks at first, then monthly for two years.

The key in this study is that the war has just begun. Participants must be within the first 100 days of diagnosis of type 1 diabetes. Albright has diabetes, but has not yet reached the point of needing insulin shots. But doctors know he will.

“Sometimes it takes only a few weeks, sometimes it can take a few years, but in the end with type 1 diabetes, all the insulin-producing cells are destroyed. What we are trying to do is to rescue at least some percentage of the cells,” said William Russell, M.D., director of the Division of Pediatric Endocrinology at the Monroe Carell Jr. Children's Hospital at Vanderbilt and Vanderbilt's principal investigator for the Type 1 Diabetes TrialNet studies.

In autoimmune disorders, certain triggers in the immune system are overactive and can cause the immune system to become destructive. Doctors now know this is one of the mechanisms involved in the destruction of insulin-producing cells (beta cells) in type 1 diabetes.

Abatacept, or CTLA-4 immunoglobulin (Ig), is already approved to quell the autoimmune disorder rheumatoid arthritis in children. CTLA4-Ig binds to a crucial trigger in the T cells of the immune system. The hope is by continually tying up the triggers through regular infusions of Abatacept, the immune system will be quieted and insulin-producing beta cells will be spared.

“If you can preserve some of the indigenous production of insulin, it is much easier to control blood sugar levels and prevent some of the long-term and devastating effects of the disease than if you try to control blood sugars in a completely artificial manner,” Russell said.

In the Abatacept trial, there must be healthy, surviving beta cells in the pancreas. Patients must still be able to produce 10 percent to 30 percent of their own insulin. Now doctors will learn if the drug can hold that line for an extended period of time.

The Albright family hopes so. Already two of the four children in the family have fully insulin-dependant type 1 diabetes. The family enrolled in the TrialNet studies when their daughter, Sarah, 9, was diagnosed in August. Their youngest son, Michael, was the first diagnosed, in 2003. He is now 13. Only the eldest child, 19-year-old Jonathan, remains free of any signs or markers for the disease.

“When Daniel was first tested, he had two markers that made him high risk to develop diabetes. He had diabetes within a year,” said Donna Albright. “It's a challenge having children with diabetes. There was a lot of getting up at 3 a.m. to test Michael's blood sugar. Now he has a pump. We hope Daniel might not get to that point.”

“These families are so enthusiastic and committed. They come from all over — Tennessee, Georgia, Mississippi and beyond — and they commit to years of regular visits at our clinic for testing infusions and checkups,” Russell said.

The TrialNet study coordinators at Vanderbilt, Margo Black, R.N., and Anne Brown, A.P.N., say enrollment is complete for the Abatacept trial, but they anticipate adding new trials as they become available. The Vanderbilt Eskind Pediatric Diabetes Clinic now follows more than 1,900 children with diabetes and sees about 250 new cases each year.