Condition category
Nutritional, Metabolic, Endocrine
Date applied
07/02/2007
Date assigned
01/03/2007
Last edited
28/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Ezio Bonifacio

ORCID ID

Contact details

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

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 measures

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

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

http://tu-dresden.de/die_tu_dresden/fakultaeten/medizinische_fakultaet/index_html/document_view?cl=en

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

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25898052

Publication citations

Additional files

Editorial Notes