INIT II

The Intranasal Insulin Trial (INIT II) began in late 2006, and is being run by an Australian non-profit organization, the Diabetes Vaccine Development Centre (DVDC). The aim of the trial is to test a new preventative treatment for type 1 diabetes in young people who are at risk of developing this condition.

INIT II is a randomized, double-blind, placebo-controlled multi-centre clinical trial, which will determine whether intranasal insulin can delay or prevent the onset of type 1 diabetes in children and young adults at risk.

Pre-clinical Evidence
There is evidence from a mouse model of type 1 diabetes that the administration of intranasal insulin can reduce the immune attack on the insulin-producing beta cells of the pancreas, thus acting as a vaccine against the condition. In pre-clinical tests, insulin was administered onto the nasal mucosa of mice with a genetic predisposition to type 1 diabetes. This caused the induction of regulatory T-cells, which were protective against the destruction of beta cells in the mice.

INIT I
The predecessor of INIT II, the INIT I trial was designed to test safety. 38 individuals were treated with either intranasal insulin spray or placebo, daily for 10 days, and then 2 days a week for 6 months. The trial showed that intranasal insulin does not accelerate the onset of diabetes. An immune effect was also observed in children and young adults at risk of type 1 diabetes. Intranasal insulin produced effects that suggested a change in the immune attack on the insulin-producing beta cells.

Trial design
Based on the success of INIT I, the INIT II trial will test whether intranasal insulin can delay or prevent type 1 diabetes in a larger population.

Eligibility
A significant feature of the INIT II trial is the recruitment of people at risk for type 1 diabetes. The trial requires 300 participants, aged between 4 and 30. To enter the treatment arm of the trial, participants must have two or more antibodies (against insulin, GAD65, and tyrosine phosphatase-like insulinoma antigen 2), but a normal response in a glucose tolerance test. This indicates that they are in the process of developing type 1 diabetes, but significant destruction of the pancreatic beta cells has not yet occurred.

To find enough eligible people, relatives of people with type 1 diabetes are screened for antibodies. Those who are positive undergo a glucose tolerance test to make sure they do not already have diabetes. Although type 1 diabetes can be hereditary, the probability that a family member of someone with type 1 diabetes will meet the criteria to enter the trial is only around 2-3%. It is therefore expected that over 20,000 people will need to be screened.

Treatment arm
After screening, participants are staged into a treatment arm. One group receives placebo solution, and the other two receive a solution that contains one of two doses of insulin: either 40IU or 440IU. The treatment is self-administered using a nasal spray every morning for 7 consecutive days, and then once a week for 12 months. During this time, participants are monitored every four months, then every six months for a further four years.

The trial will take place at a number of centers across Australia and New Zealand, including, Other hospitals based in Sydney and Melbourne are expected to become active trial sites in 2008.
 * Mater Children’s Hospital, Brisbane
 * Women’s and Children’s Hospital, Adelaide
 * Princess Margaret Hospital, Perth
 * Royal Melbourne Hospital, Melbourne
 * North Shore Hospital, Sydney
 * Canberra Hospital, Canberra
 * Liggins Institute, Auckland, New Zealand
 * Christchurch Hospital, New Zealand

Endpoint
The primary clinical endpoint of INIT II is the development of type 1 diabetes. This is expected to be lower in participants who were exposed to insulin.