Islet autoantigen-derived peptides eluted from Human Leucocyte Antigen (HLA) class II molecules as vaccines for the immunotherapy of type 1 diabetes: a safety and proof of concept study in man
| ISRCTN | ISRCTN20254161 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20254161 |
| Secondary identifying numbers | PI/1-s |
- Submission date
- 10/02/2006
- Registration date
- 03/03/2006
- Last edited
- 17/05/2011
- 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
Not provided at time of registration
Contact information
Dr Colin Dayan
Scientific
Scientific
University of Bristol
Dorothy Hodgkin Building
Whitson street
Bristol
BS1 3NY
United Kingdom
| Phone | +44 (0)117 9283553 |
|---|---|
| Colin.dayan@bristol.ac.uk |
Study information
| Study design | Open label, phase 1, dose-escalating safety study with control (no treatment) arm (safety). T cell responses will also be measured (blinded) (proof of concept) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study objectives | Type 1 diabetes mellitus is an autoimmune condition resulting in the destruction of pancreatic beta cells, leading to a failure of insulin production. Hypotheses: To determine in man whether intradermal administration of a soluble peptide sequence of proinsulin (C19-A3) identified by microelution from HLA-DR4 molecules and shown to be a disease-related T cell epitope by responses in newly-diagnosed patients with diabetes: 1. Is safe, particularly in terms of hypersensitivity reactions over a wide dose range (10 - 100 micrograms) (safety) 2. Can induce a regulated immune response in man (loss of peptide-specific interferon (IFN) gamma+ T cells, induction of peptide specific interleukin-10+ (IL-10+) T cells (proof of concept) |
| Ethics approval(s) | Central and South Bristol Research Ethics Committee on the 16/12/2005 (ref: 05/Q2006/55). |
| Health condition(s) or problem(s) studied | Type 1 diabetes mellitus |
| Intervention | A peptide corresponding to amino-acid C19-A3 of proinsulin will be administered in increasing doses, 10, 100 and 1000 micrograms intradermally in the upper arm. Subjects will be divided into three equal groups, one group for each dose of peptide. Beginning at 10 micrograms, injections will be given on three occasions one month apart before progressing to the next dose in a new group of subjects. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Vaccine proinsulin (C19-A3) |
| Primary outcome measure | 1. Adverse event and side-effect profiles of peptide administration 2. Changes in proinsulin peptide-induced IFN-gamma+ or IL-10 response (ratio of maximal stimulation indices) as detected by Enzyme-Linked Immunosorbent Spot (ELISPOT) three months after the first injection compared to baseline |
| Secondary outcome measures | 1. Change in proinsulin peptide induced IFN-gamma+ or IL-10 response ratio six months after the first injection 2. Changes in IFN-gamma+ or IL-10 response ratio to epitopes of GAD65 and IA-2 eluted from HLA-DR4 3. Changes in IL-2, IL-4+ and IL-5+ T cell responses to the antigen panel 4. Changes in anti-insulin, proinsulin, GAD65 and IA-2 antibody levels versus baseline |
| Overall study start date | 19/12/2005 |
| Completion date | 31/12/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 72 |
| Key inclusion criteria | 1. HLA-DRB1 0401 positive patients 2. Aged 18 - 50 with type 1 diabetes of five or more years duration 3. HbA1c less than 10% and no insulin C-peptide production |
| Key exclusion criteria | 1. C-peptide response to glucagon stimulation test greater than 2 nmol/l 2. Proliferative or pre-proliferative retinopathy or macula oedema 3. Diabetic nephropathy or other severe diabetic complications 4. Asthma 6. Atopy 7. Documented allergy 8. Use of steroids or immunosuppressive drugs 9. Other autoimmune diseases (except thyroiditis) 10. Women not taking effective contraception |
| Date of first enrolment | 19/12/2005 |
| Date of final enrolment | 31/12/2007 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Bristol
Bristol
BS1 3NY
United Kingdom
BS1 3NY
United Kingdom
Sponsor information
Diabetes Vaccine Development Centre (Australia)
Research organisation
Research organisation
School of Population Health
University of Melbourne
Melbourne
3010
Australia
| Phone | +61 (0)3 8344 0753 |
|---|---|
| dirving@dvdc.org.au |
Funders
Funder type
University/education
University of Melbourne (Australia) - Diabetes Vaccine Development Centre (protocol no: PI/1-S)
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 | 01/02/2009 | Yes | No |
