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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00336674




Registration number
NCT00336674
Ethics application status
Date submitted
12/06/2006
Date registered
14/06/2006
Date last updated
30/05/2018

Titles & IDs
Public title
Trial of Intranasal Insulin in Children and Young Adults at Risk of Type 1 Diabetes
Scientific 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
Secondary ID [1] 0 0
INIT II
Universal Trial Number (UTN)
Trial acronym
INITII
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Intranasal insulin
Other interventions - Placebo

Active Comparator: DV001 - 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.

Placebo Comparator: Placebo - 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 interventions: Intranasal insulin
440IU Insulin

Other interventions: Placebo
Placebo insulin carrier solution containing benzalkonium chloride and glycerol

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
1 year of treatment 9 years follow up
Secondary outcome [1] 0 0
B cell function - Measured as glucose and insulin responses in Oral glucose tolerance test (OGTT) 6 monthly
Timepoint [1] 0 0
1 year of treatment 9 years follow up
Secondary outcome [2] 0 0
Insulin Action - Insulin resistance measured by Homeostasis of model assessment - resistance (HOMA-R) 6 monthly
Timepoint [2] 0 0
1 year of treatment 9 years follow up
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
1 year of treatment 9 years follow up

Eligibility
Key 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. -
Minimum age
4 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

-

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Mater Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
5006 - North Adelaide
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment postcode(s) [5] 0 0
6840 - Subiaco
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Melbourne Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/show/NCT00336674
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leonard C Harrison, MBBS MD DSc
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications