Effects of Recombinant Human Glutamic Acid Decarboxylase . . . - Full Text View

Sponsors and Collaborators:	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
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00529399

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 II Phase III

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Aluminum hydroxide Algeldrate Aluminum Alum, potassium Aluminum sulfate Glutamic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
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

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:	December 2008
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.
2: Experimental 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.
3: Placebo Comparator 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.

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:	8 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 8 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 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

Contacts and Locations

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

Sponsors and Collaborators

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

Investigators

Principal Investigator:	Jerry Palmer, M.D.	University of Washington
Study Chair:	Jay Skyler, M.D.	University of Miami

More Information

Related Info This link exits the ClinicalTrials.gov site

Publications:

Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001 Jul 21;358(9277):221-9. Review. Erratum in: Lancet. 2001 Sep 1;358(9283):766.

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.

Responsible Party:	NIDDK ( Ellen Leschek )
Study ID Numbers:	GAD65
Study First Received:	September 12, 2007
Last Updated:	August 20, 2008
ClinicalTrials.gov Identifier:	NCT00529399
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

immune tolerance
immunotherapy
antigen-specific tolerance
vaccine induced tolerance
Beta-cell function
T-cells
DPT-1

treatment of type 1 diabetes
new onset type 1 diabetes
juvenile diabetes
T1D
diabetes mellitus
Type 1 diabetes TrialNet
TrialNet

Study placed in the following topic categories:

Aluminum sulfate
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Disease Progression
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Aluminum Hydroxide

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Physiological Effects of Drugs

Adjuvants, Immunologic
Antacids
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009