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Effects of Recombinant Human Glutamic Acid Decarboxylase . . .

This study has been completed.
Sponsor:
Collaborators:
American Diabetes Association
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00529399
First received: September 12, 2007
Last updated: May 30, 2013
Last verified: May 2013

September 12, 2007
May 30, 2013
February 2009
May 2012   (final data collection date for primary outcome measure)
The primary outcome is the area under the stimulated C-peptide curve (AUC) over tghe first 2 years of a 4-hour mixed meal tolerance test (MMTT). [ Time Frame: Based on MMTT conducted at the two year visit ] [ Designated as safety issue: No ]
Insulin production (C-peptide secretion) [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00529399 on ClinicalTrials.gov Archive Site
Difference in loss of 2 hr peak C-peptide <0.2 pmol/ml; Mean HbA1c, insulin dose (units/kg), blood glucose ; prevalence of autoantibody positivity ; rates of severe hypoglycemic and adverse events. [ Time Frame: Comparison of values repeated over time per protocol ] [ Designated as safety issue: No ]
  • Diabetes related outcomes (i.e. HbA1c, insulin dose, hypoglycemic events) [ Time Frame: 2 years ]
  • Immunologic related outcomes (i.e. effects of GAD-Alum on humoral and T-cell reactivity) [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Effects of Recombinant Human Glutamic Acid Decarboxylase . . .
Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects

The purpose of this study is to determine whether treatment with multiple injections of GAD-Alum will preserve the body's own (endogenous) insulin production in patients who have been recently diagnosed with type 1 diabetes mellitus (T1DM).

Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part of the body which helps fight infections) mistakenly attacks and destroys the cells that produce insulin (islet cells found in the pancreas called islet cells). As these cells are destroyed, the body's ability to produce insulin decreases. Glutamic acid decarboxylase (GAD) is one of the major autoantigens (a protein that the immune system is reacting to) involved in the autoimmune process underlying T1DM.

GAD-Alum is Recombinant human (rhGAD65) and is used as an antigen-specific immune modulator. Previous studies have shown that it may slow or prevent autoimmune destruction of pancreatic islet cells by introducing "immune tolerance". By administering excess autoantigen, the body may stop its attack on its own cells that produce insulin. If the immune system's attack can be halted in a patient with recent onset T1DM, than residual insulin secretion may be maintained. This may be beneficial in decreasing acute and long-term diabetic complications as well as improving glucose control.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
  • Drug: GAD-Alum
    Participants will receive 3 injections of 20 micrograms GAD-Alum subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.
    Other Name: Diamyd
  • Drug: GAD-Alum
    Participants will receive 3 injections subcutaneously. The first two will contain 20 micrograms GAD-Alum vaccine and are given 4 weeks apart. The third injection will be Aluminum hydroxide alone and will be given 8 weeks after the second injection.
    Other Name: Diamyd
  • Drug: Aluminum hydroxide
    Participants will receive 3 injections of Aluminum hydroxide alone, subcutaneously. The first two injections are given 4 weeks apart and the second and third are given 8 weeks apart.
    Other Name: Alhydrogel
  • Experimental: 1
    3 injections of GAD-Alum vaccine
    Intervention: Drug: GAD-Alum
  • Experimental: 2
    2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
    Intervention: Drug: GAD-Alum
  • Placebo Comparator: 3
    3 injections of Aluminum hydroxide alone
    Intervention: Drug: Aluminum hydroxide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
126
May 2012
May 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 3 to 45 years - Insulin dependent type 1-diabetes mellitus diagnosed within the previous 3 months
  • Stimulated C-peptide levels greater than or equal to 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted 3 weeks from diagnosis of diabetes
  • Presence of GAD65 antibodies
  • At least one month from last immunization
  • Willing to comply with intensive diabetes management
  • If participant is a woman with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test
  • Willing to forgo routine clinical immunizations during the first 100 days after initial study drug administration

Exclusion Criteria:

  • Immunodeficiency or clinically significant chronic lymphopenia
  • Active infection
  • Positive PPD test result
  • Pregnant or lactating or anticipating becoming pregnant for 24 months following first injection
  • Ongoing use of medications known to influence glucose tolerance
  • Require use of systemic immunosuppressant(s)
  • Serologic evidence of current or past HIV, Hep B, or Hep C infection
  • History of malignancies
  • Ongoing use of non-insulin pharmaceuticals to affect glycemic control
  • Participation in another clinical trial with a new chemical entity within the past 3 months
  • Complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk including neurological, or clinically significant blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia)
  • History of epilepsy, head trauma or cerebrovascular accident or clinical
  • History of alcohol or drug abuse
Both
3 Years to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00529399
GAD65 (IND)
Yes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • National Center for Research Resources (NCRR)
  • American Diabetes Association
  • Juvenile Diabetes Research Foundation
Principal Investigator: Diane Wherrett, M.D. University of Toronto, Hospital for Sick Children
Study Chair: Jay Skyler, M.D. University of Miami
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
May 2013

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