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Effects of Recombinant Human Glutamic Acid Decarboxylase . . .
This study is currently recruiting participants.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), January 2010
First Received: September 12, 2007   Last Updated: January 21, 2010   History of Changes
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators: 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

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

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

Inclusion Criteria:

  • Age 3 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00529399

Contacts
Contact: Jay S Skyler, MD 305-243-6146 jskyler@miami.edu
Contact: Lisa E Rafkin, MS 305-243-6146 lrafkin@miami.edu

Locations
United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94305
Contact: Trudy Esrey, RN     650-498-4450     tesray@stanford.edu    
Principal Investigator: Darrell Wilson, MD            
Childrens Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Mary Halvorson, RN     323-669-4606     mhalvorson@chla.usc.edu    
Principal Investigator: Roshanak Monzavi, MD            
University of California-San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Celia Hamilton, RN     415-476-5026     hamiltonc@peds.ucsf.edu    
Principal Investigator: Stephen Gitelman, MD            
United States, Colorado
Barbara Davis Center for Childhood Diabetes/University of Colorado Health Sciences Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Susan George, RN     303-724-7501     Susan.George@ucdenver.edu    
Principal Investigator: Peter Gottleib, MD            
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Laurie Feldman     203-737-2760     laurie.feldman@yale.edu    
Principal Investigator: Kevan Herold, MD            
United States, Florida
University of Miami/ Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Della Matheson, RN     305-243-3781     dmatheso@miami.edu    
Principal Investigator: Jennifer B Marks, MD            
University of Florida Recruiting
Gainesville, Florida, United States
Contact: Roberta Cook, RN     352-334-0865     cookrb@peds.ufl.edu    
Principal Investigator: Desmond Schatz, MD            
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Martha Mendez, RN     317-278-8879     mwmendez@iupui.edu    
Principal Investigator: Henry Rodriquez, MD            
United States, Massachusetts
Joslin Diabetes Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Debbie Conboy, RN     617-732-2647     Debbie.Conboy@joslin.harvard.edu    
Principal Investigator: Tihamer Orban, MD            
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Jennifer Smith, RN     612-624-6682     smit5759@umn.edu    
Contact: Theresa Albright-Fischer, RN     612-626-2182     albr0088@umn.edu    
Principal Investigator: Tony Moran, MD            
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Ellen Greenberg, MPH     212-851-5425     emg25@columbia.edu    
Principal Investigator: Robin S Goland, MD            
United States, Pennsylvania
Childrens Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Karen Riley, RN     412-692-5210     karen.riley@chp.edu    
Principal Investigator: Dorothy Becker, MD            
United States, Texas
University of Texas/Southwestern Medical School Recruiting
Dallas, Texas, United States, 75390-8858
Contact: Marilyn Alford, RN     214-648-3816     Marilyn.Alford@UTSouthwestern.edu    
Principal Investigator: Philip Raskin, MD            
United States, Washington
Benaroya Research Institute Recruiting
Seattle, Washington, United States, 98101
Contact: Marli McCulloch     206-515-5233     Marli@benaroyaresearch.org    
Principal Investigator: Carla Greenbaum, MD            
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Lesley A Eisel, RN     416-813-7654 ext 1798     lesley.eisel@sickkids.ca    
Principal Investigator: Diane Wherrett, MD            
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:
Responsible Party: NIDDK ( Ellen Leschek )
Study ID Numbers: GAD65
Study First Received: September 12, 2007
Last Updated: January 21, 2010
ClinicalTrials.gov Identifier: NCT00529399     History of Changes
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
Type 1 diabetes TrialNet
immune tolerance
immunotherapy
antigen-specific tolerance
vaccine induced tolerance
Beta-cell function
T-cells
DPT-1
T1D
diabetes mellitus
TrialNet

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

ClinicalTrials.gov processed this record on February 08, 2010