- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01536431
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)
Phase 1b Study of Proinsulin (PI) Peptide Immunotherapy in New-Onset Type 1 Diabetes
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
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Bristol, United Kingdom
- Bristol Royal Infirmary
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Cardiff, United Kingdom
- University Hospital of Wales
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London, United Kingdom
- Guy's Hospital
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Newcastle, United Kingdom
- Royal Victoria Hospital
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England
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Chester, England, United Kingdom, CH2 1UL
- Countess of Chester
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-40 years.
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
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),
- Diagnosis of Type 1 diabetes within the last 100 days (dated from the first insulin injection).
- Possession of *0401 allele at the HLA-DRB1 gene locus
- At least one positive islet cell autoantibody (ie anti-GAD65, antibodies to insulinoma-associated antigen-2 (IA-2) or zinc transporter 8 (ZnT8)).
- Peak insulin C-peptide >200 pmol/L (at any time point after stimulation with Mixed Meal Tolerance Test).
- Written and witnessed informed consent to participate.
Exclusion Criteria:
- Females who are pregnant, breast-feeding or not using adequate forms of contraception.
- Use of immunosuppressive or immunomodulatory therapies, including systemic steroids within 1 month prior to randomisation and any monoclonal antibody therapy given for any indication.
- Any other medical condition which, in the opinion of investigators, could affect the safety of the subject's participation.
- 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.
- 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
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).
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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).
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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).
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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)
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Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety
Time Frame: 3 years
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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.
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3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Allergy and hypersensitivity
Time Frame: 3 years
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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.
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3 years
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Safety of frequent dosing
Time Frame: 3 years
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To explore the safety of extending peptide treatment to more frequent dosing (2-weekly) and for a longer time period (6 months)
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3 years
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Protective effects of insulin preservation
Time Frame: 3 years
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To provide preliminary data on any protective effect on preservation of insulin production after 1 year of treatment
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3 years
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T cell (immune) response to islet cell antigens
Time Frame: 3 years
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To provide preliminary data on changes in the T cell (immune) response to islet cell antigens in newly-diagnosed patients following PI peptide treatment.
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3 years
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Mark Peakman, MBBS BSc MSc PhD FRCP, King's College Hospital NHS Trust
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPON817-10
- 2007-003759-35 (EudraCT Number)
- 66760879 (Registry Identifier: ISRCTN)
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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