NCT03182322

Brief Summary

Type 1 diabetes (T1D) results from an autoimmune destruction of the insulin-producing beta cells. Administration of mucosal insulin in islet autoantibody-negative children who are genetically predisposed for T1D offers the potential for inducing immunological tolerance to beta cells and thereby protect against the development of islet autoimmunity and T1D. Intranasal insulin has the advantage that whole protein will be exposed at the mucosa. Therefore, the available dose of insulin when administered intranasally is likely to be consistent between individuals. On this basis, the investigators aim to conduct a placebo-controlled, double-blind/double-masked primary intervention pilot trial (PINIT Study) of intranasal insulin treatment in islet autoantibody negative children to test immune efficacy and safety in the primary prevention setting. This pilot will help to develop and design a Phase III study aiming to test efficacy of preventing islet autoimmunity and T1D.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2018

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 8, 2017

Completed
3 months until next milestone

First Posted

Study publicly available on registry

June 9, 2017

Completed
12 months until next milestone

Study Start

First participant enrolled

May 25, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 7, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 7, 2021

Completed
Last Updated

June 22, 2021

Status Verified

June 1, 2021

Enrollment Period

3 years

First QC Date

March 8, 2017

Last Update Submit

June 21, 2021

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 diabetesT1Ddiabetes mellitusintranasal insulinmucosal toleranceautoantigenself tolerancepreventionat risk for developing type 1 diabetesjuvenile diabetes

Outcome Measures

Primary Outcomes (1)

  • The activation of an immune response (antibody or CD4+ T cell) against insulin.

    The responses are as previously defined in the Pre-POINT study (JAMA 313:1541-9). An antibody response is defined as serum IAA positivity in the competitive immuno-precipitation assay, an increase from baseline (\>10 cpm) in serum IgG binding to insulin, or a positive salivary IgA binding to insulin. A CD4+ T cell response is defined as a stimulation index \>3 and a \>2-fold increase from stimulation index at baseline. A positive response (responder) will be defined as a child with an antibody or T cell response to insulin at any time point during treatment. The number of responders in the insulin treated group will be compared with the number of responders in the placebo treated group.

    change from baseline (visit 1) in CD4+ T cell response measured as a stimulation index at 3 months (visit 2) and 6 months (visit 3) of treatment

Other Outcomes (13)

  • Hypoglycemia

    Measured at baseline (visit 1) and at each subsequent visit at 3 months (visit 2) and 6 months (visit 3) of treatment.

  • GAD, IA-2 and ZnT8 autoantibodies

    Measured at baseline and at 3 months, 6 months.

  • Gene expression analysis of single cells.

    baseline, 3 months and 6 months

  • +10 more other outcomes

Study Arms (2)

intranasal insulin

EXPERIMENTAL

rH-insulin formulation and for a dose of 440 IU insulin to the nasal mucosa. Treatment will be administered daily for the first 7 intervention days, and one day per week thereafter for 6 months.

Drug: intranasal insulin

intranasal placebo

PLACEBO COMPARATOR

Treatment with placebo nasal spray daily for the first 7 intervention days and one day per week thereafter for 6 months.

Other: Placebo

Interventions

intranasal insulinDRUG

Total of 6 months treatment; daily for the first 7 intervention days and one day per week thereafter (formulation containing rH-insulin, benzalkonium chloride, glycerol and water)

intranasal insulin
PlaceboOTHER

Total of 6 months treatment; daily for the first 7 intervention days and one day per week thereafter placebo (formulation containing benzalkonium chloride, glycerol and water)

intranasal placebo

Eligibility Criteria

Age1 Year - 7 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Children aged 1 year to 7 years (randomization must be performed prior to 8th birthday) who
  • have the HLA DR3-DQB1\*0201/DR4-DQB1\*0302 or the HLA DR3-DQB1\*0201/DR4-DQB1\*0304 genotype or
  • have a first degree relative with type 1 diabetes, and have a HLA genotype that includes the HLA DR4-DQB1\*0302 or HLA DR4-DQB1\*0304 haplotype, and does not include one of the following alleles DR 11, DR 12, DQB1\*0602, or haplotypes DR7-DQB1\*0303, DR14-DQB1\*0503, DR13-DQB1\*0603 and must be
  • Islet autoantibody negative (autoantibodies against insulin, GAD, IA-2 and ZnT8) at time of screening.

You may not qualify if:

  • Concomitant disease or treatment, which may interfere with assessment or cause immunosuppression, as judged by the investigators.
  • Any condition that could be associated with poor compliance.
  • Any defect or pathology of nasal passage, which would preclude application of the intranasal spray.
  • Any moderate to severe intolerance to ingredients of the investigational medicinal product.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Klinik und Poliklinik für Kinder und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany

Dresden, 01307, Germany

Location

Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Lehrstuhl für Diabetes und Gestationsdiabetes der Technischen Universität München

München, 80804, Germany

Location

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Peter Achenbach, PD Dr.

    Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Lehrstuhl für Diabetes und Gestationsdiabetes, der Technischen Universität München, Kölner Platz 1, 80804 München, Germany

    PRINCIPAL INVESTIGATOR

  • Anette-G. Ziegler, Prof. Dr.

    Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Lehrstuhl für Diabetes und Gestationsdiabetes, der Technischen Universität München, Kölner Platz 1, 80804 München, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2017

First Posted

June 9, 2017

Study Start

May 25, 2018

Primary Completion

June 7, 2021

Study Completion

June 7, 2021

Last Updated

June 22, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will not share

Locations

DE(2)