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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Melbourne Health
ClinicalTrials.gov Identifier:
NCT00336674
First received: June 12, 2006
Last updated: May 11, 2015
Last verified: May 2015
  Purpose

In people with type I 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.


Condition Intervention Phase
Type 1 Diabetes
Biological: Intranasal insulin
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Melbourne Health:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • B cell function: measured as glucose and insulin responses in Oral glucose tolerance test (OGTT) 6 monthly. [ Time Frame: 1 year of treatment 9 years follow up ] [ Designated as safety issue: No ]
  • Insulin Action: Insulin resistance measured by Homeostasis of model assessment - resistance (HOMA-R) 6 monthly. [ Time Frame: 1 year of treatment 9 years follow up ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 year of treatment 9 years follow up ] [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: December 2006
Estimated Study Completion Date: December 2024
Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Recombinant 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.
Biological: Intranasal insulin
440IU Insulin
Placebo Comparator: 2
Placebo 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.
Other: Placebo
Placebo insulin carrier solution containing benzalkonium chloride and glycerol

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 .

  Eligibility

Ages Eligible for Study:   4 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. First-degree or second-degree relative of a person with Type 1 diabetes (T1D) diagnosed before age 40.
  2. Age 4-30 years if first-degree relative; age 4-20 years if second-degree relative.
  3. Confirmed serum antibodies to two or more islet antigens.
  4. Normal oral glucose tolerance test (OGTT).
  5. 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)
  6. Provision of written consent. -

Exclusion Criteria:

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

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336674

Locations
Australia, Australian Capital Territory
Canberra Hospital
Canberra, Australian Capital Territory, Australia, 2606
Australia, New South Wales
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
The Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Mater Children's Hospital
Brisbane, Queensland, Australia, 4101
Australia, South Australia
Womens and Childrens Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Royal Children's Hospital
Melbourne, Victoria, Australia, 3052
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Australia, Western Australia
Princess Margaret Hospital
Subiaco, Western Australia, Australia, 6840
New Zealand
University of Auckland
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Sponsors and Collaborators
Melbourne Health
Investigators
Principal Investigator: Leonard C Harrison, MBBS MD DSc Melbourne Health
  More Information

No publications provided

Responsible Party: Melbourne Health
ClinicalTrials.gov Identifier: NCT00336674     History of Changes
Other Study ID Numbers: INIT II
Study First Received: June 12, 2006
Last Updated: May 11, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Melbourne Health:
Type 1 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 01, 2015