Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects - Full Text View

Purpose

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	Intervention	Phase
Type 1 Diabetes Mellitus	Drug: Anti-CD20 (rituximab)	Phase II Phase III

MedlinePlus related topics:

Diabetes Diabetes Type 1

ChemIDplus related topics:

Insulin Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

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

Primary Outcome Measures:

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

Secondary Outcome Measures:

Area under the 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)

Estimated Enrollment:	66
Study Completion Date:	December 2006

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.

Eligibility

Ages Eligible for Study:	12 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Between the ages of 12 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00279305

Locations


United States, California
	Childrens Hospital of Los Angeles
	Los Angeles, California, United States, 90027
	Stanford University
	Stanford, California, United States, 94305
	University of California-San Francisco
	San Francisco, California, United States, 94143

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
	Joslin
	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
	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

Australia
	Walter and Eliza Hall Institute of Medical Research
	Victoria, Australia

Canada, Ontario
	The Hospital for Sick Children
	Toronto, Ontario, Canada, M5G 1X8

Italy
	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)

National Institute of Child Health and Human Development (NICHD)

American Diabetes Association

Juvenile Diabetes Research Foundation

Investigators


Principal Investigator:	Mark Pescovitz, MD	Type 1 Diabetes TrialNet

More Information

NIDDK/Type 1 Diabetes Clinical Trials This link exits the ClinicalTrials.gov site

Type 1 Diabetes TrialNet This link exits the ClinicalTrials.gov site

American Diabetes Association This link exits the ClinicalTrials.gov site

Juvenile Diabetes Foundation International This link exits the ClinicalTrials.gov site

Publications:

Pescovitz MD. The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant. 2004 Feb;8(1):9-21. Review.

Noorchashm H, Noorchashm N, Kern J, Rostami SY, Barker CF, Naji A. B-cells are required for the initiation of insulitis and sialitis in nonobese diabetic mice. Diabetes. 1997 Jun;46(6):941-6.

Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, Jankovic M, Pierani P, De Stefano P, Bonora MR, Locatelli F. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003 May 15;101(10):3857-61. Epub 2003 Jan 16.

Binstadt BA, Caldas AM, Turvey SE, Stone KD, Weinstein HJ, Jackson J, Fuhlbrigge RC, Sundel RP. Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr. 2003 Nov;143(5):598-604. Erratum in: J Pediatr. 2004 Apr;144(4):558.

Edwards JC, Leandro MJ, Cambridge G. B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun. 2005;8:175-92.

Sidner RA, Book BK, Agarwal A, Bearden CM, Vieira CA, Pescovitz MD. In vivo human B-cell subset recovery after in vivo depletion with rituximab, anti-human CD20 monoclonal antibody. Hum Antibodies. 2004;13(3):55-62.

Bearden CM, Agarwal A, Book BK, Vieira CA, Sidner RA, Ochs HD, Young M, Pescovitz MD. Rituximab inhibits the in vivo primary and secondary antibody response to a neoantigen, bacteriophage phiX174. Am J Transplant. 2005 Jan;5(1):50-7.

Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81.

Serreze DV, Silveira PA. The role of B lymphocytes as key antigen-presenting cells in the development of T cell-mediated autoimmune type 1 diabetes. Curr Dir Autoimmun. 2003;6:212-27. Review. No abstract available.

Study ID Numbers:	Ritux
First Received:	January 17, 2006
Last Updated:	June 19, 2008
ClinicalTrials.gov Identifier:	NCT00279305
Health Authority:	United States: Food and Drug Administration

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

T1D

Study placed in the following topic categories:

Autoimmune Diseases

Diabetes Mellitus, Type 1

Rituximab

Disease Progression

Diabetes Mellitus

Endocrinopathy

Metabolic disorder

Glucose Metabolism Disorders

Insulin

Additional relevant MeSH terms:

Metabolic Diseases

Immunologic Factors

Immune System Diseases

Antineoplastic Agents

Therapeutic Uses

Physiological Effects of Drugs

Endocrine System Diseases

Antirheumatic Agents

Pharmacologic Actions

ClinicalTrials.gov processed this record on July 03, 2008

Sponsors and Collaborators:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Child Health and Human Development (NICHD) American Diabetes Association Juvenile Diabetes Research Foundation
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00279305