No 'Vaccination' Effect Seen in Children at Risk for Diabetes

Norra MacReady

June 14, 2017

SAN DIEGO — A small pilot study testing a "vaccine" against type 1 diabetes in children has yielded disappointing results, according to new findings presented here at the American Diabetes Association (ADA) 2017 Scientific Sessions.

Two injections of alum-formulated glutamate decarboxylase (alum-GAD, Diamyd), administered 30 days apart, did not delay or prevent the development of diabetes in the participants, compared with children in the control group, principal investigator Helena Elding Larsson, MD, PhD, said during a press conference on type 1 diabetes prevention.

But this may not be the end of the road. "Other doses or combinations with immunomodulatory agents or other antigens may be tested," Dr Larsson said. "We will continue to analyze the immunological samples from these patients to learn more about the mechanisms involved in this process."

First Study of Alum-GAD in Young Children

Type 1 diabetes progresses in stages, Dr Larsson explained. Stage 1 occurs when patients develop antibodies to glutamate decarboxylase, an islet-cell enzyme, plus one more islet-cell antibody. There are no clinical symptoms of the disease at this stage, and blood sugar is still normal.

Stage 2 is characterized by abnormal glucose tolerance plus the autoantibodies, and stage 3 is when the clinical diagnosis is made. Previous small studies indicated that therapy with alum-GAD was associated with preservation of islet-cell function in patients in the early stages of diabetes development, but this hasn't been confirmed in large trials, she noted.

For this study, Dr Larsson, associate professor of pediatric endocrinology and diabetes, Lund University, Sweden, and colleagues randomized 50 children at stages 1 or 2 to receive either alum-GAD or a placebo.

The children ranged in age from 4 to 18 years. Recruitment occurred from May 2009 to January, 2012. The patients were then followed for 5 years.

The children had a median age of 5.2 years. At the time of enrollment, 26 (52%) already had impaired glucose tolerance, although none had yet progressed to frank type 1 diabetes. They were randomized to receive either alum-GAD in two doses of 20 µg delivered subcutaneously 30 days apart or a placebo. Oral and intravenous glucose tolerance tests were administered prior to the injections and then every 6 months during the follow-up period.

No study-related or serious adverse events occurred in any of the patients, and alum-GAD was not associated with a faster progression to diabetes or the development of any other autoimmune disease.

However, said Dr Larsson, "We could not find a significant effect in delaying or preventing type 1 diabetes in this study." By year 5, 18 children had developed type 1 diabetes, with no significant difference between the two groups (= .573).

In a press statement from Diamyd, Dr Larsson adds: "The trial is small and since fewer individuals than expected developed type 1 diabetes during the period, it may have affected the ability to detect differences in treatment effect."

Diamyd lists four trials as ongoing with the anti-GAD vaccine.

Despite these findings, the search for prevention strategies for and effective early treatment of diabetes must continue, Carla J Greenbaum, MD, director of the diabetes research program at the Benaroya Research Institute, Seattle, said at the press conference.

"Just as we treat high blood pressure as early as possible: we are trying to prevent stroke and heart disease. With diabetes, we know that when people are at stage 1, about 35 to 50 out of 100 will go on to develop clinical type 1 diabetes, and we want to intervene before there are clinical consequences."

Dr Larsson received partial funding from Diamyd Medical to perform the trial. Dr Greenbaum has served as an advisor for Lilly, Novo Nordisk, Bristol Meyers Squib, and Pfizer, and receives research funding from Janssen and Novo Nordisk.

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American Diabetes Association 2017 Scientific Sessions. Press Conference on Type 1 Diabetes Prevention; June 12, 2017; San Diego, California.

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