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Diabetes Prevention - Immune Tolerance (DIAPREV-IT)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01122446
First Posted: May 13, 2010
Last Update Posted: March 9, 2017
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.
Collaborator:
Region Skane
Information provided by (Responsible Party):
Helena Elding Larsson, Lund University
  Purpose

A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies

Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.

Objectives:

DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.

The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.

The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.


Condition Intervention Phase
Prediabetes Type 1 Diabetes Other: Placebo comparator Drug: Diamyd Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Double-blind, Randomized Investigator-initiated Study to Determine the Safety and the Effect of Diamyd® on the Progression to Type 1 Diabetes in Children With Multiple Islet Cell Autoantibodies

Resource links provided by NLM:


Further study details as provided by Helena Elding Larsson, Lund University:

Primary Outcome Measures:
  • Safety [ Time Frame: During 5 years follow up from treatment ]
    Adverse events, serious adverse events, hematology, chemistry, autoantibody titles by treatment group


Secondary Outcome Measures:
  • Time to type 1 diabetes [ Time Frame: During 5 years follow up from treatment ]
    Onset of Type 1 diabetes, defined according to ADA criteria, by treatment

  • Change in fasting glucose [ Time Frame: During 5 year follow-up from treatment ]
    Fasting glucose is measured at baseline and every 6 months within the study. 2 hour glucose at OGTT is analysed at baseline and annually in the study. Glucose is analysed by Hemocue.

  • Change in 120 minutes glucose on OGTT [ Time Frame: During 5 year follow-up from treatment ]
    OGTT is performed at baseline, after 6 months and thereafter annually

  • Change in AUC glucose on OGTT [ Time Frame: During 5 year follow-up from treatment ]
    OGTT is performed at baseline, after 6 months and thereafter annually

  • Change in fasting C-peptide [ Time Frame: During 5 year follow-up from treatment ]
    Fasting C-peptide is performed at baseline and thereafter every 6 months

  • Change in 120 min C-peptide on OGTT [ Time Frame: During 5 year follow-up from treatment ]
    OGTT is performed at baseline, after 6 months and thereafter annually

  • Change in AUC C-peptide on OGTT [ Time Frame: During 5 year follow-up from treatment ]
    OGTT is performed at baseline, after 6 months and thereafter annually

  • HbA1c [ Time Frame: During 5 year follow-up ]
    At all visits in the study HbA1c is measured. The change in HbA1c from baseline HbA1c is analysed at Laboratory of Clinical Chemistry, Skåne University Hospital, Malmö

  • change in first-phase insulin response on IvGTT [ Time Frame: During 5 year follow-up from treatment ]
    As secondary variables of effect we will measure the change in first-phase insulin response. In all children a baseline IvGTT is performed and after that annual IvGTT´s are performed within the study. First phase insulin response is calculated from insulin 1 and 3 minutes after the given glucose solution. Insulin is measured by Laboratory of Clinical Chemistry at Skåne University Hospital, Malmö. Change in first phase insulin response will be calculated for each individual and compared between the groups.


Enrollment: 50
Actual Study Start Date: April 2009
Study Completion Date: December 2016
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo comparator
Two doses of placebo day 1 and 30
Other: Placebo comparator

Placebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies.

Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo.

Active Comparator: Alum-GAD (Diamyd)
20 microgram Diamyd day 1 and 30
Drug: Diamyd

20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies.

Post diagnosis: Two doses of Diamyd followed to children originally receiving Diamyd

Other Name: Alum-GAD

Detailed Description:

A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies

Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.

Objectives:

DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.

The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.

The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.

Procedure:

50 children will be randomized to 2 injections of Diamyd® or placebo. In DIAPREV-IT we will use the previously tested dose of 20 µg Diamyd® administered as a prime-and-boost at days 1 and 30, as no serious adverse reactions have been observed with this regimen. The children will be followed every 3rd month for 5 years. Before the first injection of study drug both intravenous (IvGTT) and oral (OGTT) glucose tolerance test will be performed. These will be repeated during the study with OGTT every 6 month visit and IvGTT every full year visit.

Safety variables:

Collection of adverse events, serious adverser events, hematology, chemistry, titles of autoantibodies.

Effect variables:

The cumulative incidence of diabetes onset over time since randomization within each treatment group will be estimated using the Kaplan-Meier method (proportion surviving diabetes-free as a function of time).

Secondary efficacy variables:

Change in first-phase insulin response and K-value on IvGTT from baseline Change in fasting, 120 minutes and AUC C-peptide levels on OGTT Change in fasting, 120 minutes and AUC glucose on OGTT Change in HbA1c from baseline All measures during 5 years follow-up.

Children developing diabetes in the study will be offered to participate in a postdiagnosis protocol. Children who have had two doses of active Diamyd in the main study will be given one additional dose of 20 microgram Diamyd followed by one dose of placebo after 30 days. Children who have had two doses of placebo will be given two doses of 20 microgram Diamyd with 30 days in between. Post diagnosis follow up will proceed for at least 15 months from the first post diagnosis injection with collection of adverse events and metabolic evaluation with Mixed meal tolerance tests.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Children from four (4) years of age and participating in DiPiS, TEDDY or Trial Net.
  2. Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb or IAA).
  3. Written informed consent from the child and the child's parents or legal acceptable representative(s) according to local regulations.

Exclusion Criteria:

  1. Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted).
  2. Diabetes.
  3. Treatment with any oral or injected anti-diabetic medications.
  4. Significantly abnormal hematology results at screening.
  5. Clinically significant history of acute reaction to vaccines or other drugs.
  6. Treatment with any vaccine, other than influenza, within one month prior to the first dose of the study drug or planned treatment with vaccine up to two months after the last injection with the study drug.
  7. A history of epilepsy, serious head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles.
  8. Participation in other clinical trials with a new chemical entity within the previous 3 months.
  9. Significant illness other than diabetes within 2 weeks prior to first dosing.
  10. Known human deficiency virus (HIV) or hepatitis.
  11. Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigators makes the patient non-eligible for the study.
  12. Diabetes-protective HLA-DQ6-genotype.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01122446


Locations
Sweden
Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11
Malmö, Sweden, 205 02
Sponsors and Collaborators
Lund University
Region Skane
Investigators
Principal Investigator: Helena Elding Larsson, MD, PhD Region Skåne and Lund University
  More Information

Publications:
Responsible Party: Helena Elding Larsson, MD PhD, Lund University
ClinicalTrials.gov Identifier: NCT01122446     History of Changes
Other Study ID Numbers: DIAPREV/2008
First Submitted: May 12, 2010
First Posted: May 13, 2010
Last Update Posted: March 9, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Helena Elding Larsson, Lund University:
Alum-GAD
Type 1 diabetes
prevention
immune tolerance
glucose tolerance
glutamate decarboxylase autoantibodies

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Autoantibodies
Immunologic Factors
Physiological Effects of Drugs