Additional identifiers
EudraCT number
2005-001621-29
ClinicalTrials.gov number
Protocol/serial number
80804002
Study information
Scientific title
Primary intervention with mucosal insulin for prevention of type one diabetes in infants at high genetic risk to develop diabetes
Acronym
Pre-POINT (Primary Oral INsulin Trial)
Study hypothesis
Oral 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
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)
Study design
Randomised placebo-controlled double-blind/double-masked multi-centre dose-escalation primary intervention pilot study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Type 1 diabetes-associated development of autoimmunity
Intervention
Current 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 type
Drug
Phase
Not Applicable
Drug names
Insulin
Primary outcome measure
The 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 measures
1. Safety and bioavailability of mucosal insulin
2. Determination of an appropriate route and dose for insulin
Overall trial start date
01/11/2008
Overall trial end date
31/12/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current 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
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
25
Participant exclusion criteria
1. 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
Recruitment start date
01/11/2008
Recruitment end date
31/12/2013
Locations
Countries of recruitment
Austria, Germany, Italy, Switzerland, United Kingdom, United States of America
Trial participating centre
DFG-Center for Regenerative Therapies Dresden
Dresden
01307
Germany
Sponsor information
Organisation
Medical Faculty Carl Gustav Carus (Germany)
Sponsor details
Dresden University of Technology
Fetscherstr. 74
Dresden
01307
Germany
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Juvenile Diabetes Research Foundation (JDRF) (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
German Federal Ministry of Education and Research (Bundesministerium Für Bildung und Forschung [BMBF]) (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25898052