Condition category
Nutritional, Metabolic, Endocrine
Date applied
10/02/2006
Date assigned
03/03/2006
Last edited
17/05/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19040615

Publication citations

  1. 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.

Additional files

Editorial Notes