If This Vaccine Becomes an Approved Treatment It May Prevent Type 1 Diabetes
Potential new vaccine may prevent onset of Type 1 Diabetes. Results of new pilot study on Type 1 Diabetes Insulin vaccine leads to Stage 3 Clinical Trials.
A new study in the Journal of American Medicine (JAMA) on the efficacy of administering escalating doses of oral insulin to children at risk for developing Type 1 diabetes has led to approval for stage 3 clinical trials. The Pre-POINT study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 randomized clinical pilot study was the collaborative effort of scientists from Germany, Austria, the United Kingdom and the United States, headed by Ezio Bonifacio, Ph.D., from the German Research Association (DFG) Center for Regenerative Therapies Dresden (CRTD) and was conducted from 2009 thru 2013.(1)
The premise to the study, according to Bonifacio, is that by giving oral insulin to children who are at risk for Type 1 diabetes which is an auto-immune disorder, the treatment may have a vaccine like effect for the immature immune system and prevent development of the disease. He believes treatment should be started around age 6 months and continued until age 2 or 3 when the period of increased risk is over.
The study included 25 qualifying participants, ages 2 to 7, 15 of whom were female, and considered at risk for developing Type 1 diabetes because of having 2-first degree relatives with the disease and the genotype or a sibling with Type 1 diabetes and the genotype. The children then received either insulin crystals or a placebo. Study medication was provided as identical capsules containing either insulin crystals (2.5, 7.5, 22.5, or 67.5 mg) (Lilly Pharmaceuticals) in microcrystalline cellulose (total content of capsule, 200 mg) or a 200-mg microcrystalline cellulose placebo. Parents were instructed to sprinkle the contents of 1 capsule onto 1 teaspoon of glucose-containing food for administration once daily.
According to the protocol, “children in the insulin group were randomized to receive insulin in 1 of 5 study blocks. Children in block 1 were assigned to receive 2.5 mg of insulin for 6 months, followed by 7.5 mg for 3 to 12 months; those in block 2 received 2.5 mg for 6 months, followed by 22.5 mg for 3 to 12 months; those in block 3 received 7.5 mg for 6 months, followed by 67.5 mg for 3 to 12 months; those in block 4 received 22.5 mg for 3 to 12 months; and those in block 5 received 67.5 mg for 3 to 12 months. The doses were not adjusted for body weight.”(2)
Medication adherence was assessed by family self-reporting of daily capsule administration using adherence sheets and blood sugar levels were assessed by capillary blood glucose at home monitoring as well as follow up clinic visits at scheduled intervals of 2 weeks, 3 months, and 6 months after starting treatment and at 2 weeks, 3 months, 6 months, and 12 months after dose escalation.(2)
Prior to beginning the study and at follow up clinic visits, blood samples were collected for complete blood cell count and liver function tests; measurement of levels of blood urea, electrolytes, blood glucose, IgE, and islet autoantibodies; quantification of lymphocyte subsets; and measurement of T-cell responses to insulin. Saliva was collected for measurement of salivary IgA-insulin antibodies.(2)
The protocol mandated that any child who developed antibodies to glutamic acid decarboxylase 65 (GAD65) or insulinoma-associated antigen 2 (IA-2) or diabetes must stop treatment.
While there were no significant adverse effects such as development of diabetes and the findings appear to be consistent with the notion that oral exposure to an antigen can promote regulatory T-cell responses to the antigen, the Pre-Point Study was extremely limited due to a number of reasons:
- Small sample size of participants
- Age range of participants (2-7 years of age) was not indicative of population who typically develop Type 1 diabetes (peak incidence of 9 months to 2 years of age experience islet autoantibody seroconversion)
- Study did not represent children with a lower genetic risk
- Follow up duration was short
- Insufficient assay testing of immune response without external validation of assays
- Additional prior low dose treatment with insulin needed to determine response at higher dose
The results of the pilot study demonstrated that daily oral administration of 67.5 mg of insulin, compared with placebo, resulted in an immune response without hypoglycemia which is promising, however more expansive long term phase 3 clinical studies need to be conducted to determine whether oral insulin can prevent islet autoimmunity and diabetes in at risk children.
1. Type 1 diabetes prevention: insulin vaccine undergoes second trial - Institute of Diabetes Research
2. Effects of High-Dose Oral Insulin on Immune Responses in Children at High Risk for Type 1 Diabetes - The Pre-POINT Randomized Clinical Trial
3. Daily Oral Insulin Could Help Prevent Type 1 Diabetes
***For future related story... Enterovirus may be behind increase in rates of Type 1 Diabetes.