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

NCT ID: NCT01536431

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-02-28

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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pro insulin peptide

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

Group Type: EXPERIMENTAL

Pro insulin peptide

Intervention Type: DRUG

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

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).

Group Type: ACTIVE_COMPARATOR

Pro insulin peptide

Intervention Type: DRUG

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).

Saline

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls)

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).

Interventions

Pro insulin peptide

Patients will receive 10 micro gr of the peptide every 2 weeks (12 doses).

Intervention Type: 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).

Intervention Type: DRUG

Saline

Patients will receive 0 micro gr of peptide, but have saline injections every 2 weeks (controls).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Diabetes Vaccine Development Centre

OTHER

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Cardiff University

OTHER

Sponsor Role: lead

Responsible Party

Professor Colin Dayan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Peakman, MBBS BSc MSc PhD FRCP

Role: STUDY_DIRECTOR

King's College Hospital NHS Trust

Locations

Countess of Chester

Chester, England, United Kingdom

Bristol Royal Infirmary

Bristol, , United Kingdom

University Hospital of Wales

Cardiff, , United Kingdom

Guy's Hospital

London, , United Kingdom

Royal Victoria Hospital

Newcastle, , United Kingdom

Countries

United Kingdom

Other Identifiers

2007-003759-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

66760879

Identifier Type: REGISTRY

Identifier Source: secondary_id

SPON817-10

Identifier Type: -

Identifier Source: org_study_id