• 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 ]

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.

• Drug: GAD-Alum
• Drug: Aluminum hydroxide

• Experimental: 3 injections of GAD-Alum vaccine
• Experimental: 2 injections of GAD-Alum vaccine and one injection with Aluminum hydroxide alone
• Placebo Comparator: 3 injections of Aluminum hydroxide alone

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• Pleau JM, Fernandez-Saravia F, Esling A, Homo-Delarche F, Dardenne M. Prevention of autoimmune diabetes in nonobese diabetic female mice by treatment with recombinant glutamic acid decarboxylase (GAD 65). Clin Immunol Immunopathol. 1995 Jul;76(1 Pt 1):90-5.
• Tian J, Clare-Salzler M, Herschenfeld A, Middleton B, Newman D, Mueller R, Arita S, Evans C, Atkinson MA, Mullen Y, Sarvetnick N, Tobin AJ, Lehmann PV, Kaufman DL. Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. Nat Med. 1996 Dec;2(12):1348-53.
• Tisch R, Liblau RS, Yang XD, Liblau P, McDevitt HO. Induction of GAD65-specific regulatory T-cells inhibits ongoing autoimmune diabetes in nonobese diabetic mice. Diabetes. 1998 Jun;47(6):894-9.
• Tisch R, Wang B, Weaver DJ, Liu B, Bui T, Arthos J, Serreze DV. Antigen-specific mediated suppression of beta cell autoimmunity by plasmid DNA vaccination. J Immunol. 2001 Feb 1;166(3):2122-32.
• Jun HS, Chung YH, Han J, Kim A, Yoo SS, Sherwin RS, Yoon JW. Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase. Diabetologia. 2002 May;45(5):668-76. Epub 2002 Apr 4.

Inclusion Criteria:

• Age 16 to 45 years (later on the study plans to enroll younger teens and children)
• 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 within 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
• Must weigh at least 25 kg at study entry
• 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

• 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