In late 2006, the Diabetes Vaccine Development Centre commenced a clinical trial called the Type 1 Diabetes Prevention Trial (INIT II) of a new preventive treatment for type 1 diabetes for young people at risk of developing this condition. If successful, it could prevent diabetes and the need for daily insulin injections.

If you have a relative with type 1 diabetes you may be able to help us discover whether this experimental vaccine can prevent or delay the onset of type 1 diabetes.

To find out how please go to the Type 1 Diabetes Prevention Trial.

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease in which the body's own immune system attacks and destroys the insulin-producing beta cells in the pancreas and causes a lack of insulin in the body. Without insulin, the cells of the body are unable to use glucose (sugar) and the level of glucose in the blood increases and causes symptoms of diabetes.

Type 1 diabetes is one of the most costly and chronic of the childhood diseases. To stay alive, people with type 1 diabetes must take insulin injections and test their blood sugar levels multiple times a day. Even with insulin, this form of diabetes can result in reduced quality of life and can shorten the life span.

Type 1 diabetes is usually diagnosed in children below the age of 15 years, but can occur at any age. Rarely, prior to diagnosis, children can become very ill as the blood sugar rises due to the lack of insulin resulting in nausea, dehydration, weight loss and blood poisoning (known as ketoacidosis).

An estimated 140,000 people in Australia have type 1 diabetes and the International Diabetes Federation estimates there are 16 million people with type 1 diabetes worldwide.

Type 1 diabetes accounts for 42% of all the dollars spent on diabetes treatment in Australia even though people with type 1 diabetics only account for 10% of the diabetes population.

An individual with type 1 diabetes will take around 65,000 injections and measure their blood glucose levels over 80,000 times in a lifetime.

In March 2003, the National Health and Medical Research Council jointly funded the Diabetes Vaccine Development Centre (DVDC) in collaboration with the New York-based Juvenile Diabetes Research Foundation (International).

This centre was a $10 million dollar initiative and has been part of a coordinated global effort to develop a vaccine for type 1 diabetes.

In late 2006, the DVDC commenced a clinical trial called the Type 1 Diabetes Prevention Trial (INIT II) of a new preventive treatment for type 1 diabetes for young people at risk of developing this condition.

If successful, it could prevent diabetes and the need for daily insulin injections.

Type 1 Diabetes Prevention Trial

The Type 1 Diabetes Prevention Trial (Intranasal Insulin Trial - INIT II) is a multi-centre, randomised, double-blind, placebo controlled trial which will determine whether intranasal administration of insulin to children and young adults at risk of type 1 diabetes will delay or prevent the onset of type 1 diabetes.

There is significant evidence suggesting that the administration of intranasal insulin can reduce the immune attack on the insulin producing cells thus acting as a vaccine against type 1 diabetes. This approach has shown promise in both preclinical and early stage clinical testing. The INIT I trial demonstrated an acceptable safety profile and an immune effect resulting from the administration of intranasal insulin in children and young adults at risk of type 1 diabetes. 38 individuals were treated with either intranasal insulin spray or placebo for 10 days and then 2 days a week for 6 months. The trial results suggested that intranasal insulin does not accelerate the onset of diabetes and does produce changes suggesting a change in the immune attack on the insulin producing cells. Based on that success, the Type 1 Diabetes Prevention Trial (INIT II) will test whether intranasal insulin can delay or prevent type 1 diabetes in a larger population.

A significant feature of the Type 1 Diabetes Prevention Trial (INIT II) is the recruitment of people at risk for type 1 diabetes. In order to find 300 participants, aged between 4 and 30 for the trial, we will test 20,000 first and second-degree relatives of people with type 1 diabetes. This is because only about two per cent of family members will have a high enough risk of diabetes to be eligible to enter the trial.

Patients taking part in the trial will self administer the insulin solution or placebo using a nasal spray every morning for 7 consecutive days and then once a week for 12 months. They will then be monitored for a further four years.

The trial will take place at a number of centres across Australia and New Zealand. Centres will include:

Mater Children’s Hospital, Brisbane
Women’s and Children’s Hospital, Adelaide
Princess Margaret Hospital, Perth
Royal Melbourne Hospital, Melbourne
Royal North Shore Hospital, Sydney
Canberra Hospital, Canberra
Liggins Institute, Auckland, New Zealand
Christchurch Hospital, New Zealand
Other hospitals based in Sydney and Melbourne are expected to become active trial sites in the coming months.

A person will be eligible to enter the trial if they: have a first-degree relative (mother or father, brother or sister, son or daughter) or a second-degree relative (grandmother or grandfather, aunt or uncle, niece or nephew, half-sister or half-brother) with type 1 diabetes; are aged between 4 and 30 years; and have a positive blood test for antibodies against components of the beta cells known as autoantigens.

Genes (DNA) play a significant role in type 1 diabetes. People with a close family member (blood relative) with type 1 diabetes have a 10-15 times greater risk of developing the condition than those without. The immune damage to the beta cells that results in type 1 diabetes is thought to begin months to years before the lack of insulin causes symptoms.

In order to find approximately 300 high-risk participants for the trial, over 20,000 first and second-degree relatives of people with type 1 diabetes need to be tested for antibodies against components of the beta cells. This is because only about two per cent of family members will have a high enough risk of diabetes to be eligible to enter the trial.

Type 1 Diabetes Prevention Trial (Intranasal Insulin Trial - INIT II)

The Type 1 Diabetes Prevention Trial (INIT II) is divided into three phases:

Screening Phase
Staging Phase
Clinical Trial Phase

During the Screening Phase a person will be eligible to enter the trial if they: have a first-degree relative (mother or father, brother or sister, son or daughter) or a second-degree relative (grandmother or grandfather, aunt or uncle, niece or nephew, half-sister or half-brother) with type 1 diabetes; are aged between 4 and 30 years; and are otherwise healthy. People participating in the screening phase will be asked to have a blood test for antibodies against components of the beta cells known as autoantigens.

The Staging Phase will commence if a participant is found to have antibodies to a number of beta cell autoantigens. The small proportion of people who are eligible for this phase will be asked to attend their nearest participating clinic on two occasions. They will undergo further blood tests to see how much insulin their body produces after a dose of glucose into a vein and by mouth. These tests will refine the level of risk which the person has of developing type 1 diabetes.

The Clinical Trial Phase will test the treatment of the intranasal vaccine to see if it prevents type 1 diabetes. It involves self-administering treatment with a nasal spray every day for 7 days and then once a week for 1 year. Follow-up visits to the nearest participating clinic will be required every 3 months in the first year and every six months for 4 years after that to monitor the effects of the vaccine.

During the Clinical Trial Phase two doses of the experimental treatment will be tested against a placebo (inactive dummy spray). Participants will be randomly assigned to receive one of three treatments: either 40IU insulin, 440IU insulin or placebo. The chance of any participant getting one of the insulin doses is two in three (67%), and the chance of getting the placebo is one in three (33%). During the trial neither the participants nor the researchers will be aware of which treatment is being used. All new conventional medicines and drugs are tested in this way before they can be approved by Government regulatory bodies.

What is the point of this trial?

In this trial we are hoping to find a way to stop Type 1 Diabetes before any symptoms develop. We are trying to find people who are already developing the disease but have no symptoms yet. In these people, it might be possible that a once-weekly nasal spray could prevent or delay the need for insulin injections.

Who can enter?

There are quite specific entry criteria (see the "Participation" section) but in general this trial is for people who have a close relative with Type 1 Diabetes, because these people are at higher risk of developing Type 1 Diabetes themselves.

Why should I (or my kids) enter this trial?

There are several good reasons why you might want to join Type 1 Diabetes Prevention Trial (INIT II).

First, if you are related to someone with Type 1 Diabetes, you are in a unique position to contribute to the future prevention of this illness. We hope that some day, nobody will have to use insulin injections to control the symptoms of Type 1 Diabetes.

Second, if you are at risk of Type 1 Diabetes, it pays to check for the antibodies that signal the disease has begun:

If you are producing the antibodies, and you decide to continue in the trial, the nasal spray of insulin could potentially help to delay your need for insulin injections.
If you are producing the antibodies, but decide not to continue in the trial, you will at least know to monitor yourself for Type 1 Diabetes symptoms.
If you discover you aren’t producing the Type 1 Diabetes antibodies, you will not be eligible to continue in the trial, but we hope you will have gained some peace of mind.

I thought insulin was for treating Type 1 Diabetes, so why are you giving it to people who don’t have diabetes?

Insulin is a naturally occurring hormone, made by the beta cells of the pancreas. People with Type 1 Diabetes lose these cells because of a faulty immune reaction, and stop producing insulin. They then have to use injections as a replacement.

One of the ways the immune system recognises and targets beta cells is by the insulin they produce. Evidence shows that a nasal spray of insulin can help train the immune system to tolerate insulin. We hope this will then prevent or delay the immune attack on the beta cells. The nasal insulin acts like a vaccine on the immune tissue in the membranes of the nose. It is not absorbed and therefore doesn’t affect the level of glucose (sugar) in the blood.

Isn’t it dangerous to be a clinical trial subject?

As well as experiencing the benefits of a new medicine, there may also be side effects for some people who participate in a clinical trial. The risks of participating in this study have been assessed by the Human Research Ethics Committees at each of the participating hospitals. After reviewing all the data, the committees each believe that the anticipated benefits outweigh any foreseeable risks and inconveniences.

Intranasal insulin has been used in trials in people with diabetes since the 1920s to see if insulin could be absorbed this way and lower the level of glucose (sugar) in the blood. However, it was found that intranasal insulin is not absorbed into the bloodstream unless a detergent-like “enhancer” is added to the insulin. The Type 1 Diabetes Prevention Trial (INIT II) nasal spray contains no enhancer.

Since 1980, at least 15 trials of intranasal insulin have been published, 11 of which have administered insulin with an enhancer and 4 without. In all of these, nasal irritation was non-existent to minimal and no other side-effects were noted. In the pilot Intranasal Insulin Trial I (INIT I), nasal irritation was reported by about half of participants. We believe this was caused by the preservative, which has now been changed. No other adverse effects were seen.

There is always the possibility of unforeseen risks or side effects, and it is impossible to rule these out completely. Before you agree to participate in the trial you will be provided with a full explanation of the clinical trial, written in plain English. This will explain things such as the eligibility criteria; possible risks and benefits of the new medicine; the risks of any side-effects; the type, frequency and risks of any medical tests or procedures that may be undertaken as part of the trial; and your rights and responsibilities.

If you choose to participate the doctor or study nurse will carefully monitor you throughout the study and record any problems or side effects you have, these will be relayed to the principal researcher to ensure that you are kept as safe as possible. If you experience any adverse effects, you may withdraw from the trial at any time.

What if I put my kids through this long clinical trial process, and it turns out they wouldn’t have got Type 1 Diabetes anyway?

Of all the people screened, only around 1 in 50 will be eligible for the experimental treatment. These are the people who already have two or more marker antibodies but don’t yet show symptoms. Therefore anyone eligible to enter the trial has a high risk. In the next 5 years, almost half of these people will develop the disease. Everyone else (the other 49 out of 50) will just have the initial blood test.

If my child will inevitably develop Type 1 Diabetes symptoms, we’d be happier not knowing!

Many parents whose families have a history of Type 1 Diabetes are understandably worried about the impact of this disease on their children. Of course it is frightening to think that your child faces a lifelong condition such as Type 1 Diabetes. However, we urge people to think calmly about what’s best for their child. For some who develop Type 1 Diabetes, the first sign that they are not producing enough insulin is a severe medical emergency, such as diabetic ketoacidosis that can lead to coma. Thankfully, this is relatively rare, but early detection can help to avoid such a situation, and the child can come to terms with the news over time. Studies have shown that involvement in a clinical trial can aid in early detection and reduce the proportion of people presenting with ketoacidosis. If the Type 1 Diabetes Prevention Trial (INIT II) is successful, participating may extend the time that your child remains free from worries about blood sugar.

Will I find out what treatment I am on? Will I be able to keep taking the insulin nasal spray if it works in the trial?

No. The trial is double-blind, which means that nobody connected with the trial will know what treatment you are taking—even the doctors and nurses you see as part of the trial. At the end of the study when the results have been analysed you will find out whether you received insulin or placebo. Even then, the treatment will still need approval by the federal government’s Therapeutic Goods Administration before it can be given to any potential patients.

Further enquiries...

Please contact Felicity Taylor for any further enquiries.

Please include your name and contact details in the email.

To register your interest, establish your eligibility, or learn more about the trial, register online or by phone.

To register online please visit our partner site - Type 1 Diabetes Prevention Trial (INIT II) Clinical Trial Registration Site - then download a copy of the Participant Information and Consent Form or arrange to have one mailed to you.

Signed consent forms should be sent to:

Intranasal Insulin Trial II
Reply Paid 84486
Darlinghurst NSW 2010

To speak with the Type 1 Diabetes Prevention Trial (INIT II) Call Centre by phone - 1300 138 712