Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
American Diabetes Association
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT01030861
First received: December 11, 2009
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the "pre-diabetic" state and thereby prevent or delay the onset of type 1 diabetes.


Condition Intervention Phase
Autoantibody Positive
Non-diabetic Relatives at Risk for Type 1 Diabetes
High Risk
Impaired Glucose Tolerance
Drug: Teplizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation. [ Time Frame: Elapsed time from random treatment to development of type 1 diabetes (or time of last contact among those enrolled and determined to be eligible) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • effects on teplizumab based on age, gender, race/ethnicity,weight, BMI, immunologic, genetic , demographic, and lifestyle factors. [ Time Frame: Longitudinal analysis will take place over time until diagnosis of diabetes; some secondary outcome measures will be monitored longer such as metabolic and immunological markers. ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: August 2010
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: teplizumab
Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.
Drug: Teplizumab
intravenous infusions
Placebo Comparator: Placebo infusion
Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period.
Drug: Teplizumab
intravenous infusions

Detailed Description:

The study plans to enroll approximately 140-170 subjects between the ages of 8-45 years, over 2-3 years. The study is projected to last between 4-6 years, depending upon rate of enrollment and number of subjects who develop diabetes.

The main study objective is to determine whether intervention with teplizumab will prevent or delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and other mechanistic outcomes will be assessed during the study.

  Eligibility

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

Inclusion Criteria:

  • Between ages of 8-45 years
  • Have a relative with type 1 diabetes
  • If first degree relative must be 8-45 years old (brother, sister, parent, offspring)
  • If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle, grandchild, cousin)
  • Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit [fasting blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on OGTT greater than or equal to 200 mg/dL]
  • Presence of at least two confirmed diabetes autoantibodies

Exclusion Criteria:

  • type 1 diabetes previously diagnosed or detected at screening [fasting glucose greater or equal to 126 mg/dL or 2 hour glucose greater or equal to 200 mg/dL]
  • abnormalities in blood counts, liver enzymes, INR,
  • positive PPD test

    • vaccination with live virus within 6 weeks of randomization
  • evidence of acute infection based on laboratory testing or clinical evidence
  • serological evidence of past current or past HIV , hepatitis B, or hepatitis C infection
  • Be currently pregnant or lactating
  • Prior treatment with study drug
  • Prior treatment with other monoclonal antibody in past one year
  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: NCT01030861

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
University of California in San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Christine Torok, RN    415-502-9089    TorokC@peds.ucsf.edu   
Principal Investigator: Steve Gitelman, MD         
University of California-San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Kathleen Breen, RN    415-502-8640    breenk@peds.ucsf.edu   
Principal Investigator: Stephen Gitelman, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Trudy Esrey, RN    650-498-4450    tesrey@stanford.edu   
Principal Investigator: Darrell Wilson, MD         
United States, Colorado
Barbara Davis Center for Childhood Diabetes/ University of Colorado Recruiting
Denver, Colorado, United States
Contact: Jennifer Smith    720-839-1208    jennifer.e.smith@ucdenver.edu   
Principal Investigator: Peter Gottleib, MD         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States
Contact: Laurie Feldman, MPH    203-737-2760    laurie.feldman@yale.edu   
Principal Investigator: Kevan Herold, MD         
United States, Florida
University of Florida Recruiting
Gainesvillle, Florida, United States, 32610
Contact: Jessica Ferguson, RN    352-294-0762    jaycee@ufl.edu   
Principal Investigator: Desmond Schatz, MD         
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Della Matheson, RN    305-243-3781    dmatheso@miami.edu   
Principal Investigator: Jennifer Marks, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Bonnie Jagielo, RN    317-278-2551    bjagielo@iu.edu   
Principal Investigator: Linda DiMeglio, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Christine Wong, RN    612-624-2922    kwong001@umn.edu   
Principal Investigator: Toni Moran, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Ellen Greenberg, MD    212-851-5492    emg25@columbia.edu   
Principal Investigator: Robin Goland, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15201
Contact: Kelli DeLallo, RN    412-692-5210    kelli.delallo@chp.edu   
Principal Investigator: Dorothy Becker, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: Margo Black, RN, CDE         
Principal Investigator: William Russell, MD         
United States, Texas
University of Texas Recruiting
Dallas, Texas, United States, 75390-9072
Contact: Oralenda Smith, RN    214-648-7123    oralenda.smith@utsouthwestern.edu   
Principal Investigator: Philip Raskin, MD         
United States, Washington
Benaroya Research Institute Recruiting
Seattle, Washington, United States, 982101
Contact: Marli McCulloch         
Principal Investigator: Carla Greenbaum, MD         
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, MSG-1X8
Contact: Lesley Eisel, RN    416-813-8159    lesley.eisel@sickkids.ca   
Principal Investigator: Diane Wherrett, MD         
Sponsors and Collaborators
Juvenile Diabetes Research Foundation
American Diabetes Association
Investigators
Study Chair: Kevan Herold, MD Yale School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01030861     History of Changes
Other Study ID Numbers: TrialNet - tep (IND)
Study First Received: December 11, 2009
Last Updated: March 5, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
type 1 diabetes
pre-diabetic
autoantibody positive
at risk for type 1 diabetes
glucose intolerance
relatives of people with type 1 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hyperglycemia

ClinicalTrials.gov processed this record on September 14, 2014