Primary intervention with mucosal insulin for prevention of type one diabetes in infants at high genetic risk to develop diabetes

ISRCTN ISRCTN76104595
DOI https://doi.org/10.1186/ISRCTN76104595
EudraCT/CTIS number 2005-001621-29
Secondary identifying numbers 80804002
Submission date
07/02/2007
Registration date
01/03/2007
Last edited
28/04/2015
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.diabetes-point.org/nav4uk.html

Study website

Contact information

Prof Ezio Bonifacio
Scientific

DFG-Center for Regenerative Therapies Dresden
Fetscherstr. 105
Dresden
01307
Germany

Study information

Study designRandomised placebo-controlled double-blind/double-masked multi-centre dose-escalation primary intervention pilot study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titlePrimary intervention with mucosal insulin for prevention of type one diabetes in infants at high genetic risk to develop diabetes
Study acronymPre-POINT (Primary Oral INsulin Trial)
Study objectivesOral application of insulin induces a protective immune response for the purpose of vaccination in infants at high risk of developing type one diabetes mellitus (T1DM).

Please note that as of 18/02/2010 this record has been extensively updated.
1. The intranasal arm of this trial has been removed. Italy and Switzerland have been removed from the countries of recruitment, and Canada has been added.
2. The overall trial start and end date were changed from 01/04/2007 and 30/09/2008 to 01/11/2008 and 30/06/2011, respectively.
3. The target number of participants has been reduced to 25.
4. The sponsor and contact information for this trial has changed.
Previous sponsor:
Institute for Diabetes Research at the Paediatric Clinic (Institut für Diabetesforschung an der Kinderklinik)
Munich Techical University (Technische Universität München)
Kölner Platz 1
Munich (München)
Germany

Previous contact:
Prof Anette-G Ziegler

On 09/07/2013 the overall trial end date was changed from 30/06/2011 to 31/12/2013.
Ethics approval(s)1. Ethics committee of the Bayrische Landesärztekammer, ref: 05135
2. Ethikkommission der Mediz. Univ. Wien (ref: 341/2007), NHS National Research Ethics Service, ref: 10/H0106/33, COMIRB (05-1043)
Health condition(s) or problem(s) studiedType 1 diabetes-associated development of autoimmunity
InterventionCurrent information as of 18/02/2010:
Active arm: insulin given orally at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg daily
Control arm: placebo administered orally

Initial information at time of registration:
Active arm A: insulin given orally at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg daily
Active arm B: insulin given intra-nasally at 0.28 mg, 0.83 mg, 2.5 mg, or 7.5 mg daily for ten days and twice weekly thereafter
Control arm A: placebo administered orally
Control arm B: placebo administered intra-nasally

Children will be treated for the duration of the Pre-POINT study or until becoming Glutamic Acid Decarboxylase (GAD) or IA-2 auto-antibody positive or until diabetes onset. Average expected duration of treatment: 11 months (minimum three months; maximum 18 months corresponding to expected Pre-POINT study duration).
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Insulin
Primary outcome measureThe development of immunity to insulin (Immunoglobulin G [IgG] or Immunoglobulin A [IgA] antibodies, or T-cell response to insulin and/or insulin peptides).
Secondary outcome measures1. Safety and bioavailability of mucosal insulin
2. Determination of an appropriate route and dose for insulin
Overall study start date01/11/2008
Completion date31/12/2013

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit2 Years
Upper age limit7 Years
SexBoth
Target number of participants25
Key inclusion criteriaCurrent inclusion criteria as of 09/07/2013:
1. Children aged 2 to 7 years who:
1.1. Have a multiplex first degree family history of T1DM (both parents, parent and siblings, or two siblings) and a type 1 diabetes susceptible Human Leukocyte Antigen (HLA) DR4-DQB1*0302 or DR4-DQB1*0304 haplotype and none of the following HLA DR or DQB1 alleles:
1.1.1 DR 11
1.1.2 DR 12
1.1.3 DQB1*0602
1.1.4 DR7-DQB1*0303
1.1.5 DR14-DQB1*0503
1.2. Have a sibling with T1DM and are identical by descent for the HLA DR3/DR4-DQ8 genotype with their diabetic sibling
2. Islet auto-antibody (IA-2) negative at time of recruitment

Previous inclusion criteria:
1. Children aged 2 to 7 years who:
1.1. Have a multiplex first degree family history of T1DM (both parents, parent and siblings, or two siblings) and have one of the following Human Leukocyte Antigen (HLA) genotypes:
1.1.1. DR4- DQA1*0301-DQB1*0302 / DR3- DQA1*0501-DQB1*0201
1.1.2. DR4- DQA1*0301-DQB1*0302 / DR4- DQA1*0301-DQB1*0302
1.1.3. DR4- DQA1*0301-DQB1*0302 / DR4- DQA1*0301-DQB1*0201
1.1.4. DR4- DQA1*0301-DQB1*0302 / DR4- DQA1*0301-DQB1*0304, or
1.2. Have a sibling with T1DM and are identical by descent for the HLA DR3/DR4-DQ8 genotype with their diabetic sibling
2. Islet auto-antibody (IA-2) negative at time of recruitment
Key exclusion criteria1. Children with any kind of congenital or acquired chronic disease that potentially interfere with the study objectives
2. Prior or current participation in another intervention trial
Date of first enrolment01/11/2008
Date of final enrolment31/12/2013

Locations

Countries of recruitment

  • Austria
  • Germany
  • Italy
  • Switzerland
  • United Kingdom
  • United States of America

Study participating centre

DFG-Center for Regenerative Therapies Dresden
Dresden
01307
Germany

Sponsor information

Medical Faculty Carl Gustav Carus (Germany)
University/education

Dresden University of Technology
Fetscherstr. 74
Dresden
01307
Germany

Website http://tu-dresden.de/die_tu_dresden/fakultaeten/medizinische_fakultaet/index_html/document_view?cl=en
ROR logo "ROR" https://ror.org/04za5zm41

Funders

Funder type

Charity

Juvenile Diabetes Research Foundation (JDRF) (USA)

No information available

German Federal Ministry of Education and Research (Bundesministerium Für Bildung und Forschung [BMBF]) (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 21/04/2015 Yes No
HRA research summary 28/06/2023 No No