Effects of Recombinant Human Glutamic Acid Decarboxylase on the Progression of Type 1 Diabetes in New Onset Subjects

Phase 2

Completed

Interventions: Drug: GAD-Alum and Aluminum hydroxide
Drug: GAD-Alum
Drug: Aluminum hydroxide

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: 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).

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2	GAD-Alum and Aluminum hydroxide	2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
1	GAD-Alum	3 injections of GAD-Alum vaccine
3	Aluminum hydroxide	3 injections of Aluminum hydroxide alone

Primary Outcome Measures

Name	Time	Method
The Primary Outcome is the Area Under the Stimulated C-peptide Curve (AUC) at the One Year Visit	Based on mixed meal tolerance test (MMTT) conducted at the one year visit	The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.

Secondary Outcome Measures

Name	Time	Method

Locations (15): Childrens Hospital of Los Angeles
🇺🇸
Los Angeles, California, United States
Stanford University
🇺🇸
Palo Alto, California, United States
University of California-San Francisco
🇺🇸
San Francisco, California, United States
Columbia University
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New York, New York, United States
Childrens Hospital of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Benaroya Research Institute
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Seattle, Washington, United States
University of Texas/Southwestern Medical School
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Dallas, Texas, United States
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
University of Florida
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Gainesville, Florida, United States
University of Miami/ Miller School of Medicine
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Miami, Florida, United States
Indiana University School of Medicine
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Indianapolis, Indiana, United States
Hospital for Sick Children
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Toronto, Ontario, Canada
Joslin Diabetes Center
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Boston, Massachusetts, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center
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Aurora, Colorado, United States