Safety Study to Assess Whether Proinsulin Peptide Injections Can Slow or Stop the Body Damaging Its Own Insulin-making Cells in the Pancreas in Patients Newly Diagnosed With Type 1 Diabetes (MonoPepT1De)

July 27, 2015 updated by: Professor Colin Dayan, Cardiff University

Phase 1b Study of Proinsulin (PI) Peptide Immunotherapy in New-Onset Type 1 Diabetes

The purpose of this study is to address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.

Study Overview

Detailed Description

Type 1 Diabetes (also known as insulin-dependent diabetes) is caused by destruction of the insulin producing cells (Beta Cells) in the pancreas. Our group is interested in how this destruction could be stopped or reversed, as this may lead to development of a new generation of diabetes treatments which can prevent or slow down the damage, reducing or possibly even removing there need for insulin injections.

In a previous study we examined the safety of our novel approach to this problem, proinsulin (PI) peptide immunotherapy, in longstanding diabetes patients (diagnosed more than 5 years before), and found it to be well tolerated and free of major hypersensitivity reactions. However, it remains theoretically possible that this form of immunotherapy could make the immune reaction to the insulin making cells worse rather than better.

This cannot be studied directly in longstanding patients as they have no or almost no insulin making cells left.

So,the principle objective of the current study is to address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bristol, United Kingdom
        • Bristol Royal Infirmary
      • Cardiff, United Kingdom
        • University Hospital of Wales
      • London, United Kingdom
        • Guy's Hospital
      • Newcastle, United Kingdom
        • Royal Victoria Hospital
    • England
      • Chester, England, United Kingdom, CH2 1UL
        • Countess of Chester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18-40 years.
  2. If female, must be (as documented in patient notes):

    • postmenopausal (at least 1 year without spontaneous menses)
    • surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrolment)
    • using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment
    • have a sexual partner with non-reversed vasectomy (with confirmed azoospermia)
    • be using 1 barrier method with the use of a spermicide(e.g., condom, diaphragm or cap)
    • have placement of a intra-uterine device
  3. If male, must be:

    • using a barrier method of contraception (condom) with the use of a spermicide
    • have a sexual partner using one of the methods in point 2 above or
    • have a non-reversed vasectomy (with confirmed azoospermia),
  4. Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection).
  5. Possession of *0401 allele at the HLA-DRB1 gene locus
  6. At least one positive islet cell autoantibody (ie anti-GAD65, antibodies to insulinoma-associated antigen-2 (IA-2) or zinc transporter 8 (ZnT8)).
  7. Peak insulin C-peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test).
  8. Written and witnessed informed consent to participate.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pro insulin peptide
Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).
Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).
Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).
Active Comparator: Pro insulin peptide & saline
Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).
Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).
Patients will receive 10 micro gr of the peptide monthly (ever 4 weeks, 6 doses) and saline injections monthly alternating with the peptide (2 weeks interval between the drug and saline).
Placebo Comparator: Saline
Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls)
Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 3 years
To address the safety issue of whether, in patients with newly-diagnosed diabetes who still make some insulin, proinsulin peptide therapy adversely affects the rate of damage to the insulin making cells.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Allergy and hypersensitivity
Time Frame: 3 years
To confirm that PI peptide treatment does not induce allergy or hypersensitivity and has a good safety profile in new-onset type 1 diabetes patients.
3 years
Safety of frequent dosing
Time Frame: 3 years
To explore the safety of extending peptide treatment to more frequent dosing (2-weekly) and for a longer time period (6 months)
3 years
Protective effects of insulin preservation
Time Frame: 3 years
To provide preliminary data on any protective effect on preservation of insulin production after 1 year of treatment
3 years
T cell (immune) response to islet cell antigens
Time Frame: 3 years
To provide preliminary data on changes in the T cell (immune) response to islet cell antigens in newly-diagnosed patients following PI peptide treatment.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Mark Peakman, MBBS BSc MSc PhD FRCP, King's College Hospital NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

February 14, 2012

First Submitted That Met QC Criteria

February 16, 2012

First Posted (Estimate)

February 22, 2012

Study Record Updates

Last Update Posted (Estimate)

July 28, 2015

Last Update Submitted That Met QC Criteria

July 27, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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