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Type 1 Diabetes MellitusPhase 2TN05NCT00279305

Rituximab in New Onset Type 1 Diabetes

A Phase 2 study testing Anti-CD20 (rituximab) in people with Type 1 Diabetes Mellitus, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 16 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 8 to 45 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Anti-CD20 (rituximab)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
87 participants
Where
16 sitesin 4 countries
Study dates
Aug 2005to Nov 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Have a history of malignancies
  • Currently using non-insulin pharmaceuticals that effect glycemic control
  • Currently participating in another type 1 diabetes treatment study

Trial locations and contacts

16 sites in 4 countries.

16 sites in 4 countries

United States13 sites
  • Barbara Davis Center for Childhood Diabetes

    Aurora, Colorado, 80010

  • Joslin

    Boston, Massachusetts, 02215

  • University of Texas

    Dallas, Texas, 75235-8858

  • University of Florida

    Gainesville, Florida, 32610-0296

  • Indiana University-Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Childrens Hospital of Los Angeles

    Los Angeles, California, 90027

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Columbia University

    New York, New York, 10032

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California-San Francisco

    San Francisco, California, 94143

  • Benaroya Research Institute

    Seattle, Washington, 98101

  • Stanford University

    Stanford, California, 94305

Other trials in United States

Australia1 site
  • Walter and Eliza Hall Institute of Medical Research

    Victoria

Other trials in Australia

Canada1 site
  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Italy1 site
  • San Raffaele Hospital

    Milan

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
Anti-CD20 (rituximab), Placebo Comparator
Keywords
Newly diagnosed type 1 diabetes, New Onset type 1 diabetes, Preservation of insulin secretion, Type 1 diabetes, Juvenile Onset Diabetes, Insulin Dependent Diabetes, T1D
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-CD20 (rituximab)Drug

  • Placebo ComparatorDrug

    Placebo intravenous infusion

Study groups in NCT00279305
Study groupRoleWhat they receive
Rituximab Intravenous InfusionExperimentalParticipants 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
Receives: Drug: Anti-CD20 (rituximab)
Placebo Intravenous InfusionPlacebo comparatorParticipants will receive placebo given as an intravenous infusion with 4 administrations at weeks 0, 1, 2, and 3.
Receives: Drug: Placebo Comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.

    Measured: When all participants complete the 1 year visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2006 (estimated)
  2. Study startAug 2005
  3. Primary completionApr 2009
  4. Study completionNov 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00279305
Sponsor's protocol ID
TN05 Ritux
Other IDs
U01DK061055
Acronym
TN05
Status last verified
Apr 2020
First submitted
17 Jan 2006
Last updated
6 May 2020
Data monitoring committee
Yes
Individual data sharing
Yes: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn05-anticd20/?query=tn05

Publications

  • Pescovitz MD. The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant. 2004 Feb;8(1):9-21. doi: 10.1046/j.1397-3142.2003.00135.x.

    PubMed 15009836
  • 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. doi: 10.2337/diab.46.6.941.

    PubMed 9166663
  • 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. doi: 10.1182/blood-2002-11-3547. Epub 2003 Jan 16.

    PubMed 12531800
  • 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. doi: 10.1067/s0022-3476(03)00382-2.

    PubMed 14615729
  • Edwards JC, Leandro MJ, Cambridge G. B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun. 2005;8:175-92. doi: 10.1159/000082103.

    PubMed 15564721
  • 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.

    PubMed 15598985
  • 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. doi: 10.1111/j.1600-6143.2003.00646.x.

    PubMed 15636611
  • 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. doi: 10.1056/NEJMoa032534.

    PubMed 15201414
  • 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. doi: 10.1159/000066863. No abstract available.

    PubMed 12408054
  • Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, Raskin P, Rodriguez H, Schatz DA, Wherrett D, Wilson DM, Lachin JM, Skyler JS; Type 1 Diabetes TrialNet Anti-CD20 Study Group. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009 Nov 26;361(22):2143-52. doi: 10.1056/NEJMoa0904452.

    PubMed 19940299
  • Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, Moran A, Raskin P, Rodriguez H, Schatz DA, Wherrett DK, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Anti-CD20 Study Group. B-lymphocyte depletion with rituximab and beta-cell function: two-year results. Diabetes Care. 2014 Feb;37(2):453-9. doi: 10.2337/dc13-0626. Epub 2013 Sep 11.

    PubMed 24026563

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-CD20 (rituximab) in people with Type 1 Diabetes Mellitus, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 16 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Australia, Canada, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00279305, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2020.

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