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
Contact information
Prof Ezio Bonifacio
Scientific
Scientific
DFG-Center for Regenerative Therapies Dresden
Fetscherstr. 105
Dresden
01307
Germany
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Primary intervention with mucosal insulin for prevention of type one diabetes in infants at high genetic risk to develop diabetes |
| Study acronym | Pre-POINT (Primary Oral INsulin Trial) |
| Study objectives | 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(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) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/11/2008 |
| Completion date | 31/12/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 2 Years |
| Upper age limit | 7 Years |
| Sex | Both |
| Target number of participants | 25 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/11/2008 |
| Date of final enrolment | 31/12/2013 |
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
01307
Germany
Sponsor information
Medical Faculty Carl Gustav Carus (Germany)
University/education
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" |
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 share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not 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 |
