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Rituximab in New Onset Type 1 Diabetes (TN05)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00279305
Recruitment Status : Completed
First Posted : January 19, 2006
Results First Posted : August 18, 2016
Last Update Posted : May 6, 2020
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Diabetes Association
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these beta cells, the body cannot maintain proper blood glucose levels in response to daily activities such as eating or exercise. With fewer insulin producing cells blood glucose increases, causing hunger, thirst, and unexplained weight loss. By the time these symptoms develop, 80-90% of a person's beta cells have already been destroyed. However, this also means that between 10-20% of these cells remain that continue to produce insulin.

Scientists have learned that two types of immune cells, B cells and T cells, are involved in causing type 1 diabetes. T cells are responsible for attacking and destroying the beta cells that make insulin. Although they don't attack insulin producing cells, B cells may be what trigger the T cells to attack.

This study will investigate the use of rituximab to see if it can help lower the number of immune B cells thereby preventing the destruction of any remaining insulin producing beta cells that remain at diagnosis. Rituximab is approved by the Food and Drug Administration (FDA) for the treatment of a condition called B-lymphocyte lymphoma. Its effects on the immune system are well understood through its use in organ transplantation. Research has shown that rituximab might be helpful in treating other conditions caused by T cells and B cells, including type 1 diabetes. The goal of this study is to find out if rituximab can preserve residual insulin secretion and prevent further beta cell destruction in type 1 diabetes.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: Anti-CD20 (rituximab) Drug: Placebo Comparator Phase 2

Detailed Description:

The study is a randomized, two-arm, trial in which 2/3 of participants will receive the study drug, while the remaining 1/3 will receive a placebo (a pretend medicine that does nothing). The group you are assigned to is decided by chance (as by the toss of a coin or drawing straws). Neither you nor your doctor will be able to choose which group you are in. Also, neither you nor the researchers will know which group you are in. Participants will take rituximab, or the placebo, once a week during the first 4 weeks in the study. It will be given as an intravenous infusion at a clinical center.

Participants will need to return to the clinical center for a visit about every 3 months for two years; those participants that continue to secrete insulin will have further follow-up for an additional two years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects
Actual Study Start Date : August 2005
Actual Primary Completion Date : April 2009
Actual Study Completion Date : November 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Rituximab Intravenous Infusion
Participants will receive active rituximab (anti-CD20 monoclonal antibody) as an intravenous infusion, with 4 administrations at weeks 0, 1, 2, and 3 at a dose of 375mg/m2
Drug: Anti-CD20 (rituximab)
Placebo Comparator: Placebo Intravenous Infusion
Participants will receive placebo given as an intravenous infusion with 4 administrations at weeks 0, 1, 2, and 3.
Drug: Placebo Comparator
Placebo intravenous infusion

Primary Outcome Measures :
  1. Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4-hour Mixed Meal Tolerance Test (MMTT) Administered at 1 Year [ Time Frame: When all participants complete the 1 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.

    The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   8 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Between the ages of 8 and 45 years
  • Within 3 months of diagnosis of type 1 diabetes
  • Have presence of at least one diabetes-related autoantibody
  • Must have stimulated C-peptide levels of at least 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) within one month of randomization
  • If female with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing while participating in the study
  • Have not received an immunization for at least one month
  • Must be willing to comply with intensive diabetes management
  • Must weigh at least 25 kg at study entry

Exclusion Criteria:

  • Are immunodeficient or have clinically significant chronic lymphopenia
  • Have an active infection or positive purified protein derivative (PPD) test result
  • Currently pregnant or lactating; or anticipate becoming pregnant.
  • Require chronic use of steroids
  • Have current or past HIV, hepatitis B, or hepatitis C infection
  • Have any complicating medical issues that interfere with study conduct or cause increased risk
  • Have a history of malignancies
  • Currently using non-insulin pharmaceuticals that effect glycemic control
  • Currently participating in another type 1 diabetes treatment study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00279305

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United States, California
Childrens Hospital of Los Angeles
Los Angeles, California, United States, 90027
University of California-San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80010
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0296
University of Miami
Miami, Florida, United States, 33136
United States, Indiana
Indiana University-Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas
Dallas, Texas, United States, 75235-8858
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Walter and Eliza Hall Institute of Medical Research
Victoria, Australia
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
San Raffaele Hospital
Milan, Italy
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Diabetes Association
Juvenile Diabetes Research Foundation
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Study Chair: Carla Greenbaum, MD Type 1 Diabetes TrialNet
Additional Information:
Publications of Results:
Other Publications:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00279305    
Other Study ID Numbers: TN05 Ritux
U01DK061055 ( U.S. NIH Grant/Contract )
First Posted: January 19, 2006    Key Record Dates
Results First Posted: August 18, 2016
Last Update Posted: May 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data are available at the NIDDK Central Repository:
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Newly diagnosed type 1 diabetes
New Onset type 1 diabetes
Preservation of insulin secretion
Type 1 diabetes
Juvenile Onset Diabetes
Insulin Dependent Diabetes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents