Rituximab in New Onset Type 1 Diabetes (TN05)

April 27, 2020 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

87

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Victoria, Australia
        • Walter and Eliza Hall Institute of Medical Research
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children
  • Italy
      • Milan, Italy
        • San Raffaele Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital of Los Angeles
      • San Francisco, California, United States, 94143
        • University of California-San Francisco
      • Stanford, California, United States, 94305
        • Stanford University
    • Colorado
      • Aurora, Colorado, United States, 80010
        • Barbara Davis Center for Childhood Diabetes
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University-Riley Hospital for Children
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Columbia University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75235-8858
        • University of Texas
    • Washington
      • Seattle, Washington, United States, 98101
        • Benaroya Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
When all participants complete the 1 year visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Juvenile Diabetes Research Foundation
American Diabetes Association

Investigators

  • Study Chair: Carla Greenbaum, MD, Type 1 Diabetes TrialNet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2005

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

January 17, 2006

First Submitted That Met QC Criteria

January 17, 2006

First Posted (Estimate)

January 19, 2006

Study Record Updates

Last Update Posted (Actual)

May 6, 2020

Last Update Submitted That Met QC Criteria

April 27, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TN05 Ritux
  • U01DK061055 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn05-anticd20/?query=tn05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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