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.

Background

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 [ [http://www.jem.org/cgi/content/full/184/6/2167 Harrison et al. (1996) J Exp Med 184, 2167-2174] ] .

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 [ [http://care.diabetesjournals.org/cgi/content/full/27/10/2348 Harrison et al. (2004) Diabetes Care 27, 2348-2355.] ] .

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,
*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 ZealandOther hospitals based in Sydney and Melbourne are expected to become active trial sites in 2008.

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.

References

External links

* [http://www.dvdc.org.au The Diabetes Vaccine Development Centre]
* [http://www.stopdiabetes.com.au Australian INIT II website] , [http://www.stopdiabetes.co.nz New Zealand INIT II website]