Contact information
Type
Scientific
Primary contact
Dr Colin Dayan
ORCID ID
Contact details
University of Bristol
Dorothy Hodgkin Building
Whitson street
Bristol
BS1 3NY
United Kingdom
+44 (0)117 9283553
Colin.dayan@bristol.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
PI/1-s
Study information
Scientific title
Acronym
Study hypothesis
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
Central and South Bristol Research Ethics Committee on the 16/12/2005 (ref: 05/Q2006/55).
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
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Phase I
Drug names
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 trial start date
19/12/2005
Overall trial end date
31/12/2007
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
72
Participant 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
Recruitment start date
19/12/2005
Recruitment end date
31/12/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Bristol
Bristol
BS1 3NY
United Kingdom
Sponsor information
Organisation
Diabetes Vaccine Development Centre (Australia)
Sponsor details
School of Population Health
University of Melbourne
Melbourne
3010
Australia
+61 (0)3 8344 0753
dirving@dvdc.org.au
Sponsor type
Research organisation
Website
Funders
Funder type
University/education
Funder name
University of Melbourne (Australia) - Diabetes Vaccine Development Centre (protocol no: PI/1-S)
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
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19040615
Publication citations
-
Results
Thrower SL, James L, Hall W, Green KM, Arif S, Allen JS, Van-Krinks C, Lozanoska-Ochser B, Marquesini L, Brown S, Wong FS, Dayan CM, Peakman M, Proinsulin peptide immunotherapy in type 1 diabetes: report of a first-in-man Phase I safety study., Clin. Exp. Immunol., 2009, 155, 2, 156-165, doi: 10.1111/j.1365-2249.2008.03814.x.