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Type 1 DiabetesPhase 2INITIINCT00336674

Trial of Intranasal Insulin in Children and Young Adults at Risk of Type 1 Diabetes

A Phase 2 study testing Intranasal insulin in people with Type 1 Diabetes, run by Melbourne Health at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In people with type 1 diabetes the beta cells of the pancreas no longer make insulin because the body's immune system has attacked and destroyed the beta cells. It is thought that exposure of the mucous membranes to insulin may cause act like a vaccine effect whereby protective immune cells are stimulated and these… Read more about this study

Who is it for?
Ages 4 to 30 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Intranasal insulin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
110 participants
Where
6 sitesin 2 countries
Study dates
Dec 2006to 13 Nov 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • First-degree or second-degree relative of a person with Type 1 diabetes (T1D) diagnosed before age 40.
  • Age 4-30 years if first-degree relative; age 4-20 years if second-degree relative.
  • Confirmed serum antibodies to two or more islet antigens.
  • Normal oral glucose tolerance test (OGTT).
  • First phase insulin response (FPIR) at or above threshold - Primary Stratum - greater than or equal to 10th percentile for siblings, offspring and second-degree relatives of person with T1D (greater than or equal to 100uU/ml if aged 8 or more years OR greater than or equal to 60 uU/ml if aged less than 8) and greater than or equal to the 1st percentile for parents of someone with T1D (greater than ore equal to 60uU/ml). Secondary Stratum: Greater than or equal 1st percentile, less than 10th percentile for siblings, offspring and second-degree relatives of someone with T1D (greater than or equal to 50uU/ml less than 100 uU/ml if aged greater than or equal to 8 years or greater than or equal to 20 uU/ml less than 60uU/ml if aged less than 8 years)
  • Provision of written consent. -

Who cannot join

  • History of treatment with insulin or oral hypoglycemic agents
  • Known diabetes by ADA/WHO criteria
  • Pregnant or lactating or of child-bearing potential not using an adequate method of contraception
  • Concomitant disease or treatment which may interfere with assessment or cause immunosuppression, as judged by the investigators.
  • Uncorrected vitamin D deficiency
  • Known alcohol or drug abuse, psychiatric or other condition that could be associated with poor compliance.
Show all 10Show fewer
  • Known liver disease, or persisting elevation of plasma Aspartate transaminase (AST) or Alanine transaminase (ALT) levels.
  • Impaired renal function
  • Any defect or pathology of nasal passage which would preclude application of the intranasal spray.
  • -

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Australia5 sites

  • Mater Children's Hospital

    Brisbane, Queensland, 4101

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3050

  • Womens and Childrens Hospital

    North Adelaide, South Australia, 5006

  • Princess Margaret Hospital

    Subiaco, Western Australia, 6840

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

New Zealand1 site

  • University of Auckland

    Auckland

Other trials in New Zealand

About this study

Official title: A Randomised, Double-blind, Placebo-controlled Trial of Intranasal Insulin (440 IU) in Children and Young Adults at Risk of Type 1 Diabetes: Intranasal Insulin Trial II

In people with type 1 diabetes the beta cells of the pancreas no longer make insulin because the body's immune system has attacked and destroyed the beta cells. It is thought that exposure of the mucous membranes to insulin may cause act like a vaccine effect whereby protective immune cells are stimulated and these then counteract the "bad" immune cells that damage the beta cells. This study aims to determine if intranasal insulin can protect beta cells and stop progression to diabetes in individuals who are at risk.

Read the detailed description

Autoimmune diseases are the outcome of dysregulated immune responses to self-antigens. Type 1 diabetes (T1D), previously known as insulin-dependent or juvenile diabetes, is an autoimmune disease in which the body's immune system reacts against and destroys the insulin-producing β cells in the islets of the pancreas. T1D classically affects children and young adults. Approximately 15% of people with diabetes have this form of the disease and no treatment is currently available to prevent it. Asymptomatic individuals in the pre-clinical stage of T1D can be identified by the presence of circulating antibodies to the islet autoantigens (pro)insulin, glutamic acid decarboxylase (GAD) and tyrosine phosphatase-like insulinoma antigen 2 (IA2). (Pro)insulin is the only autoantigen that is specific for β cells and several lines of evidence demonstrate that it plays a key role in driving autoimmune β-cell destruction.

The ability to use self-antigens as tools to induce protective immunity, free from the side effects of conventional non-specific immunosuppression, is the 'Holy Grail' of autoimmune disease therapy. Animal models provide proof-of-concept for such antigen-specific therapy. For example, in the non-obese diabetic (NOD) mouse, a model of spontaneous T1D, transgenic over-expression of proinsulin in antigen-presenting cells in the immune system during development or in transferred bone marrow stem cells completely prevented diabetes. On a more practical and translatable level, immune tolerance to an antigen can be achieved by administering antigen to the mucosal immune system. Thus, immune responses to antigen are suppressed by feeding antigen ('oral tolerance') or by administering antigen to the naso-respiratory mucosa .

Conditions
Type 1 Diabetes
Being tested
Intranasal insulin, Placebo
Keywords
Type 1 diabetes
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intranasal insulinBiological

    440IU Insulin

  • PlaceboOther

    Placebo insulin carrier solution containing benzalkonium chloride and glycerol

Study groups in NCT00336674
Study groupRoleWhat they receive
DV001Active comparatorRecombinant human intranasal insulin formulation in a buffered solution of benzalkonium chloride and glycerol presented in multi-dose nasal spray devices with actuators (Pfeiffer) designed to deliver 100ul spray doses to nasal mucosa. The product is formulated at a dose strength of 1100 IU / mL (40mg/mL) manufacturing formulation. The product will be self administered by eligible participants as two 100 microlitre spray doses per nostril. Treatment will be administered daily for 7 consecutive days then on one day each week for 12 months. Participants will be followed until they develop diabetes or until 5 years after the last participant has been randomised (maximum period of follow up is expected to be 10 years.
Receives: Biological: Intranasal insulin
PlaceboPlacebo comparatorPlacebo insulin carrier solution of benzalkonium chloride and glycerol presented in multi-dose nasal spray devices with actuators (Pfeiffer) designed to deliver 100ul spray doses to nasal mucosa. The product will be self administered by participants as two 100 microlitre spray doses per nostril. Treatment will be administered daily for 7 consecutive days then on one day each week for 12 months. Participants will be followed until they develop diabetes or until 5 years after the last participant has been randomised (maximum period of follow up is expected to be 10 years.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Diagnosis of Diabetes AT 5 years according to American Diabetes Association / World Health Organization (ADA/WHO) criteria.

    Defined as the presence of 2 or more of the following diagnostic criteria including diabetic fasting blood glucose level, diabetic 2 hour postprandial blood glucose level, diabetic HbA1c and symptoms

    Measured: 1 year of treatment 9 years follow up

Secondary outcomes (3)

  1. B cell function

    Measured as glucose and insulin responses in Oral glucose tolerance test (OGTT) 6 monthly

    Measured: 1 year of treatment 9 years follow up

  2. Insulin Action

    Insulin resistance measured by Homeostasis of model assessment - resistance (HOMA-R) 6 monthly

    Measured: 1 year of treatment 9 years follow up

  3. Immune function

    Measured by levels of circulating antibodies to insulin, Glutamic acid decarboxylase (GAD) and Tyrosine phosphatase - like insulinoma antigen (IA-2) and T cell responses to proinsulin, denatured insulin, GAD and tetanus at 5 years

    Measured: 1 year of treatment 9 years follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2006 (estimated)
  2. Study startDec 2006
  3. Primary completion13 Nov 2019
  4. Study completion13 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00336674
Sponsor's protocol ID
INIT II
Acronym
INITII
Status last verified
Oct 2020
First submitted
12 Jun 2006
Last updated
8 Oct 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648.

    PubMed 34091488

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Intranasal insulin in people with Type 1 Diabetes, run by Melbourne Health at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diagnosis of Diabetes AT 5 years according to American Diabetes Association / World Health Organization (ADA/WHO) criteria. (time frame: 1 year of treatment 9 years follow up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00336674, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.

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