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.|
|ClinicalTrials.gov Identifier: NCT00279305|
Recruitment Status : Completed
First Posted : January 19, 2006
Results First Posted : August 18, 2016
Last Update Posted : May 6, 2020
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|
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 (Clinical Trial)|
|Actual Enrollment :||87 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
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
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT00279305
|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, 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|
|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|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|San Raffaele Hospital|
|Study Chair:||Carla Greenbaum, MD||Type 1 Diabetes TrialNet|