Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01536431
Recruitment Status : Completed
First Posted : February 22, 2012
Last Update Posted : July 28, 2015
Sponsor:
Collaborators:
Diabetes Vaccine Development Centre
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Professor Colin Dayan, Cardiff University

Tracking Information
First Submitted Date  ICMJE February 14, 2012
First Posted Date  ICMJE February 22, 2012
Last Update Posted Date July 28, 2015
Study Start Date  ICMJE January 2012
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01536431 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2012)
  • 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.
  • 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)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Phase 1b Study of Proinsulin (PI) Peptide Immunotherapy in New-Onset Type 1 Diabetes
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE
  • Drug: Pro insulin peptide
    Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).
  • Drug: Pro insulin peptide
    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).
  • Drug: Saline
    Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).
Study Arms  ICMJE
  • Experimental: Pro insulin peptide
    Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).
    Intervention: Drug: Pro insulin peptide
  • 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).
    Intervention: Drug: Pro insulin peptide
  • Placebo Comparator: Saline
    Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls)
    Intervention: Drug: Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 27, 2015)
27
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2012)
24
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01536431
Other Study ID Numbers  ICMJE SPON817-10
2007-003759-35 ( EudraCT Number )
66760879 ( Registry Identifier: ISRCTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Professor Colin Dayan, Cardiff University
Study Sponsor  ICMJE Cardiff University
Collaborators  ICMJE
  • Diabetes Vaccine Development Centre
  • Juvenile Diabetes Research Foundation
Investigators  ICMJE
Study Director: Mark Peakman, MBBS BSc MSc PhD FRCP King's College Hospital NHS Trust
PRS Account Cardiff University
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP