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Rituximab in New Onset Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT00279305
Recruitment Status : Completed
First Posted : January 19, 2006
Results First Posted : August 18, 2016
Last Update Posted : November 2, 2016
Sponsor:
Collaborators:
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)

Tracking Information
First Submitted Date  ICMJE January 17, 2006
First Posted Date  ICMJE January 19, 2006
Results First Submitted Date  ICMJE May 12, 2016
Results First Posted Date  ICMJE August 18, 2016
Last Update Posted Date November 2, 2016
Study Start Date  ICMJE August 2005
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 17, 2006)
Area under the stimulated C-peptide curve over the first 2 hours of a 4-hour MMTT administered at 1 year
Change History Complete list of historical versions of study NCT00279305 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2006)
  • -Area under stimulated C-peptide curve over the first 2 hours of a 4-hour MMTT administered at 2 years
  • Insulin dose (units/kg) and number of injections
  • Glycosylated hemoglobin (HbA1c)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab in New Onset Type 1 Diabetes
Official Title  ICMJE Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Anti-CD20 (rituximab)
  • Drug: Placebo Comparator
    Placebo intravenous infusion
Study Arms  ICMJE
  • 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
    Intervention: 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.
    Intervention: Drug: Placebo Comparator
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 5, 2009)
87
Original Enrollment  ICMJE
 (submitted: January 17, 2006)
66
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 45 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00279305
Other Study ID Numbers  ICMJE Ritux (IND) (completed)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Study Chair: Carla Greenbaum, MD Type 1 Diabetes TrialNet
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP