Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/06/2011
Date assigned
28/07/2011
Last edited
23/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Type 1 diabetes (insulin-dependent diabetes) is caused by the body's own white blood cells damaging the insulin producing cells in the pancreas. Our aim is to develop a treatment that can slow or stop this process by switching off the white blood cells causing the damage. At present we are at quite an early stage in this research. In a previous study we were able to show in people who had had diabetes a long time that giving 3 injections of a small part of one of the molecules in the beta cells, proinsulin, appeared safe and may begin to switch off the white blood cells that are causing the damage. In this study, we are looking to see if this is also true in people who have newly-diagnosed diabetes. We will also be testing whether giving more than three injections is more effective, and whether this treatment can slow or stop the loss of insulin from the pancreas in the year after people are diagnosed.

Who can participate?
To take part you need to be aged 18-40, diagnosed with type 1 diabetes and have received your first insulin injection within 100 days of entering the trial.

What does the study involve?
If you take part, first of all, you will be asked to give a small sample of blood to test your tissue type and the antibodies to the pancreas in your blood. This sample will be taken in the same way as any standard blood test. Only around one half of people with type 1 diabetes have the right tissue type to respond to the particular fragment of proinsulin we are testing. If the first test shows you have antibodies to the pancreas and the right tissue type for the study, you will be asked to come to your local research centre for a general examination and further blood tests including a test of the amount of insulin your body still makes in the 2 hours after a standard liquid meal. If you still have some insulin response after the meal (80-90% of people do within the first year after diagnosis) you will be contacted by the research team to arrange the first injection treatment of the study. The treatments involve a very tiny, almost painless injection under the skin of the arm given in a very similar way to vaccination injections. Everyone in the trial will receive injections every 2 weeks for 24 weeks and then check-ups for another 24 weeks. People in the trial will be in one of three groups. Group A will receive only salt water injections (placebo). Group B will receive peptide injections every 4 weeks with saline injections in between. Group C will receive peptide injections every 2 weeks. Neither you nor the person giving you the injections will know until the end of the study which group you are in and which injections you are receiving. Also no one can chose which group you go into: this is done randomly by a computer programme so that everyone has an equal chance of being in any particular group. During the treatment, you will be asked to provide blood samples to test the response of your body's immune system and to pick up any side effects and on 3 occasions we will do the mixed meal tolerance test again to see how much insulin your body is making. The amounts of blood taken will be larger than usual to allow special laboratory tests to be performed. At the end of this test we will ask you for a urine sample to send to the research lab. You will not be told the results of the tests until the end of the trial unless any of the results are not normal and need treatment. The total blood volume taken from you whilst you are on the trial will be within the guidelines of the National Institute of Health, USA. Every 2 weeks you will be contacted by a nurse or doctor with training in diabetes to discuss your insulin treatment and blood sugar levels and help make sure your insulin treatment is keeping your sugar levels in a good range.

What are the possible benefits and risks of participating?
During the research project your diabetes will be very closely monitored, you will receive regular input from a nurse to help with your diabetes as well as regular check-ups including routine blood testing. If you are in the group that receives the 'active' peptide injection, it is possible that it will help keep your pancreas making insulin for longer but we cannot say this for certain until we have completed this and further research studies. There may be bruising and discomfort at the site of the blood test as with any blood test. The amounts of blood we are taking are small enough that they should not make you feel fatigue or cause anaemia. There may be local red reactions at the site of the injections. It is possible that you might have a severe reaction to the injection requiring treatment. However, we have not seen any severe reactions in the 37 people who have received this injection so far. All injections will be given with trained staff and equipment on hand if you should have any problems. If you do have a severe reaction, no further injections will be given. It is theoretically possible that if you are in the group that receives injections of 'active' peptide that they might weaken the insulin production from your pancreas. This has not been seen in previous studies and we will be testing you for insulin production every 12 weeks.

Where is the study run from?
It is being organised by Cardiff University and King's College London. There are four hospitals participating:
1. University Hospital of Wales, Cardiff
2. Guys Hospital, London
3. Bristol Royal Infirmary, Bristol
4. Royal Victoria Infirmary, Newcastle.

When is the study starting and how long is it expected to run for?
From July 2011 to February 2015.

Who is funding the study?
This study is being funded by the Diabetes Vaccine Development Centre in collaboration with the Juvenile Diabetes Research Foundation International.

Who is the main contact?
Rachel Stenson
stensonr@cardiff.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Colin Dayan

ORCID ID

Contact details

Centre for Endocrine and Diabetes Sciences
School of Medicine
Cardiff University
Heath Park
Cardiff
CF14 4XN
United Kingdom
-
dayancm@cardiff.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SPON817-10

Study information

Scientific title

Phase 1b study of proinsulin (PI) peptide immunotherapy in new onset type 1 diabetes

Acronym

MonoPepT1De-1b

Study hypothesis

The aim of the study is to examine the safety of i.d. administration of the naturally processed proinsulin peptide C19-A3 (PPI C19-A3) at a dose of 10 ìg every 14 days or every 28 days for a total of 12 and 6 doses, respectively, to patients with new-onset Type 1 diabetes
The objectives of this study are:
1. To examine the risk of C19-A3 administration in terms of general safety, induction of hypersensitivity and disease acceleration
2. To examine the effects of C19-A3 administration on appropriate biomarkers of disease (pro-inflammatory autoreactive T lymphocytes) and immune regulation (autoreactive regulatory T cells)
3. To examine any benefits of 14-day as compared to 28-day dosing

On 22/04/2015 the overall trial end date was changed from 31/12/2012 to 16/02/2015.

Ethics approval

NRES Committee South West - Exeter, REC, 25/03/2011, ref: 08/H0206/58

Study design

Multi-centre randomised double-blind placebo-controlled three-arm study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Newly diagnosed type 1 diabetes

Intervention

1. Study drug will be administered intradermally at a frequency of either bi-weekly or 4 times a week
2. To maintain blinding, all subjects will receive injections at bi-weekly intervals
3. In the case of the placebo group this will be normal saline only
4. For the Low Frequency dosing group this will be alternate study drug and normal saline only
5. For the High Frequency dosing group this will be study drug on every occasion
6. Injections will be administered over 22 weeks to achieve a total of 12
7. Thus the cumulative dose in the Low Frequency group will be 60ìg and in the High Frequency group 120 ìg

Intervention type

Drug

Phase

Phase I

Drug names

Proinsulin peptide C19-A3 (PPI C19-A3)

Primary outcome measures

Assessment of the safety of PPI C19-A3 peptide administration in subjects with new-onset Type 1 diabetes

Secondary outcome measures

1. Change in stimulated C-peptide production at 12, 24, 36 and 48 weeks versus baseline and between groups
2. Change in level or quality of T lymphocyte biomarkers of alpha cell specific immune response at 12, 24, 36 and 48 weeks versus baseline and between groups
3. Change in level or quality of islet cell autoantibody biomarkers of alpha-cell specific immune response at 12, 24, 36 and 48 weeks versus baseline and between groups
4. Change in glycated haemoglobin (as measured by % HbA1c levels), daily insulin usage, and mean amplitude of glucose excursions at 12, 24, 36 and 48 weeks versus baseline and between groups
5. Changes in the Hypoglycaemia Fear Survey (HFS), and Diabetes Treatment Satisfaction Questionnaire (DTSQs) scores at 3,6 and 12 months and ADDQoL (Audit of Diabetes-Dependent Quality of Life) at 6, and 12 months versus baseline and between groups
6. The DTSQc (Diabetes Treatment Satisfaction Questionnaire, change version) will also be compared between groups at 12 months

Overall trial start date

01/07/2011

Overall trial end date

16/02/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 18-40 years
2. Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection)
3. Possession of HLA-DRB1*04:01 allele
4. At least one positive islet cell autoantibody (ie anti-GAD65, antibodies to insulinoma-associated antigen-2 (IA-2) or zinc transporter 8 (ZnT8)).
5. Peak insulin C-peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test)
6. Written and witnessed informed consent to participate

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24

Participant exclusion criteria

1. Females who are pregnant, breast-feeding or not using adequate forms of contraception
2. Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomisation and any monoclonal antibody therapy given for any indication
3. Any other medical condition which, in the opinion of investigators, could affect the safety of the subject's participation
4. Recent subject's involvement in other research studies which, in the opinion of investigators, may adversely affect the safety of the subjects or the results of the study
5. Subjects should not have had immunisations with live or killed vaccines or allergic desensitisation procedures less than 1 month prior to their first treatment

Recruitment start date

14/02/2012

Recruitment end date

19/03/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Guy's Hospital
London
SE1 9RT
United Kingdom

Trial participating centre

Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle
NE1 4LP
United Kingdom

Sponsor information

Organisation

Cardiff University and Kings College, University of London (United Kingdom)

Sponsor details

Cardiff University
Heath Park
Cardiff
CF14 4XN
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Juvenile Diabetes Research Foundation (United Kingdom)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Diabetes Vaccine Development Centre (United Kingdom)

Alternative name(s)

DVDC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

Australia

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes