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
  Purpose

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).


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: GAD-Alum
Drug: Aluminum hydroxide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 126
Study Start Date: February 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
3 injections of GAD-Alum vaccine
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
Experimental: 2
2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
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
Placebo Comparator: 3
3 injections of Aluminum hydroxide alone
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00529399

Locations
United States, California
Childrens Hospital of Los Angeles
Los Angeles, California, United States, 90027
Stanford University
Palo Alto, California, United States, 94305
University of California-San Francisco
San Francisco, California, United States, 94143
United States, Colorado
Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
University of Florida
Gainesville, Florida, United States
University of Miami/ Miller School of Medicine
Miami, Florida, United States, 33136
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas/Southwestern Medical School
Dallas, Texas, United States, 75390-8858
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
American Diabetes Association
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Diane Wherrett, M.D. University of Toronto, Hospital for Sick Children
Study Chair: Jay Skyler, M.D. University of Miami
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00529399     History of Changes
Other Study ID Numbers: GAD65 (IND)
Study First Received: September 12, 2007
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
treatment of type 1 diabetes
new onset type 1 diabetes
juvenile diabetes
diabetes mellitus
Type 1 diabetes TrialNet
immune tolerance
immunotherapy
antigen-specific tolerance
vaccine induced tolerance
Beta-cell function
T-cells
DPT-1
T1D
TrialNet

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014