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Diabetes Mellitus, Type 1Phase 2TN02NCT00100178

New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial

A Phase 2 study testing Mycophenolate mofeteil (MMF) and Daclizumab (DZB) in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in 2 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

The objective of this study is to identify immune intervention strategies that will preserve residual beta cell function at the onset of type 1 diabetes. Scientific evidence developed over the last 10 - 20 years suggests that type 1 diabetes is a chronic, slowly progressive autoimmune disease and that clinical… Read more about this study

Who is it for?
Ages 8 to 45 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Mycophenolate mofeteil (MMF) and Daclizumab (DZB)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
126 participants
Where
11 sitesin 2 countries
Study dates
May 2004to Apr 2008
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

  • Potential participants must meet the following inclusion criteria:
  • Be within 3-months of diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria
  • Be between the ages of 8 and 45 years old
  • Must have stimulated C-peptide levels > 0.2 pmol/ml (measured during an MMTT administered no more than one month prior to the date of randomization)
  • Must have either detectable anti-GAD, anti-ICA512/IA-2, insulin autoantibodies (unless received insulin therapy for 7 days or more), or islet cell autoantibodies.
  • [The reason for inclusion of these enrollment criteria is to avoid inclusion of patients with "Type 1B diabetes mellitus", which may not involve the immunologic criteria measured by the assays that will be utilized.]
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  • If participant has reproductive potential, he or she must be agreeable to an effective form of birth control (unless abstinence is the chosen method).
  • If participant is female with reproductive potential, she must be willing to undergo pregnancy testing and to report possible or confirmed pregnancies promptly during the course of the MMF/DZB study.
  • Must be willing to comply with intensive diabetes management. The goal of management will be an HbA1c of 7.0% for all participants, regardless of age. Participants will be expected to take a sufficient number of daily insulin shots to meet this goal. Alternatively, participants can use insulin pump therapy. Participants will also be expected to test their blood sugar at least 3-4 times per day. There will be a Certified Diabetes Educator working with study participants to achieve these goals.

Who cannot join

  • Potential participants must not meet any of the following exclusion criteria:
  • Have any complicating medical issues that would interfere with blood drawing or monitoring.
  • Have a Body Mass Index (BMI) that is greater than the 95th percentile for age and gender.
  • Have serologic evidence of HIV infection.
  • Have serologic evidence of Hepatitis B infection.
  • Have serologic evidence of Hepatitis C infection.
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  • Have abnormal liver function tests.
  • Have a history of leukopenia and/or neutropenia.
  • Have a history of chronic peptic ulcer disease, erosive esophagitis, chronic inflammatory bowel disease and/or chronic colonic disease.
  • Have a positive PPD test result.
  • Have had any live vaccinations in the preceding 6 weeks (e.g. MMR-second dose, live flu vaccine, varicella vaccine, live polio vaccine, yellow fever vaccine).
  • Resides outside reasonable geographical proximity to the clinic (i.e., residence outside the state in which the Investigator and study reside, residence outside an immediately neighboring state, or residence outside an area that the Investigator considers reasonable). It is left to the Investigator's discretion to decide if a patient's geographical residence is prohibitive to complete study participation.
  • Require chronic use of steroids or other immunosuppressive agents for other conditions.
  • Be currently pregnant or 3 months postpartum.
  • Be currently nursing or within 6 weeks of having completed nursing.
  • Anticipate getting pregnant, or fathering a child, during the study.

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States10 sites

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • Barbara Davis Center for Childhood Diabetes, University of Colorado

    Denver, Colorado, 80262

  • University of Florida

    Gainesville, Florida, 32610

  • Indiana University

    Indianapolis, Indiana, 46202

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Columbia University

    New York, New York, 10032

  • University of California-San Francisco

    San Francisco, California, 94143

  • Benaroya Research Institute

    Seattle, Washington, 98101

  • Stanford University

    Stanford, California, 94305-5208

Other trials in United States

Canada1 site

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial (Preservation of Pancreatic Production of Insulin Through Immunosuppression-POPPII #1)

The objective of this study is to identify immune intervention strategies that will preserve residual beta cell function at the onset of type 1 diabetes. Scientific evidence developed over the last 10 - 20 years suggests that type 1 diabetes is a chronic, slowly progressive autoimmune disease and that clinical symptoms do not develop until at least 80% - 90% of beta cell mass has been destroyed as a result of the autoimmune process. It is now recognized that preservation of remaining beta cells is clinically important as the ability to secrete, even small amounts of insulin, can make the disease easier to control and help minimize complications associated with having years of inadequate glycemic control.

This clinical trial is the first in a series of studies to be launched by the TrialNet Study Group to test various interventions for preserving residual beta cell function in new onset type 1 diabetes. Specifically, this study is designed to determine the ability of Mycophenolate Mofetil (MMF/CellCept) used alone, or in combination with Daclizumab (DZB/Zenapax) to see if it is possible to stop the immune system from destroying beta cells in new onset type 1 diabetes patients (within 3 months of diagnosis.)

Read more

Researchers have made great strides in understanding how the immune system works and in changing the activity of immune cells with medicines called immunotherapies. Some immunotherapies work by making the immune system less active. Scientists have discovered that key immune cells, called T cells, help to cause type 1 diabetes. These T cells are largely responsible for attacking the beta cells that produce insulin. Doctors have found medicines that slow or suppress the activity of T cells. It is hoped that these immunosuppressive medicines can help treat type 1 diabetes by stopping T cells before they destroy all of the beta cells.

Medicines that make the immune system less active have been developed and studied for other diseases. Mycophenolate mofetil (MMF) and Daclizumab (DZB) are two of these medicines. Their effects on the immune system are well understood. Researchers believe these medicines may lessen the immune system's destruction of beta cells that leads to type 1 diabetes. In addition, researchers hope the effect of these medicines will last longer than other therapies.

The goal of this study is to find out if two medicines are able to stop the ongoing destruction of beta cells which are still functioning at the time type 1 diabetes is diagnosed. The two immunosuppressive medications being tested are Mycophenolate mofetil (MMF/CellCept®) and Daclizumab (DZB/Zenapax®). They work by making the immune system less active. TrialNet researchers hope that these medications will help maintain insulin secretion from remaining beta cells and thus help to maintain better glycemic control. Even if the medications work, study participants will still need to take insulin injections but it may make it easier to control normal blood sugar levels which can help reduce long-term complications of diabetes such as blindness, kidney failure, nerve damage, heart attack and stroke.

The aim is to arrest beta cell destruction in newly diabetic subjects because immune modulation may not work well alone once the autoimmune process has progressed to complete or near complete destruction of beta cells. The study's rationale is to demonstrate a meaningful preservation of islet function with minimal immune system side effects over the 4-year course of this study.

The data from this clinical trial could serve as the basis for a larger trial if the results are sufficiently positive, or they could suggest other combined intervention trials that might achieve either better efficacy or potentially preserve C-peptide without the need for continued immunosuppression.

Read the detailed description

Design of Study:

The study is a multi-center, three-arm, randomized, double-masked, placebo-controlled clinical trial. Comparisons will be made among the three groups, which are:

  • Mycophenolate mofetil active drug with Daclizumab (DZB) placebo IV
  • Mycophenolate mofetil active drug with active Daclizumab IV
  • Mycophenolate mofetil placebo with Daclizumab placebo IV

Participants that agree to enroll in the study will be asked to take study medications for two years. MMF is given by mouth twice a day. DZB is given by an intravenous infusion twice, once at the time of enrollment and again two weeks later. Both these medications are approved by the U.S. Food and Drug Administration and are used by people who have received an organ transplant. This study is testing a new use of these medications to preserve insulin secretion by delaying or stopping further destruction of insulin-secreting cells in people with newly diagnosed type 1 diabetes. Both MMF and DZB make the immune system less active. Participants will be monitored closely for any possible side effects that can occur from taking either DZB and/or MMF due to decreased activity of the immune system.

Participants will need to go to the Clinical Center for visits and tests. For the first month participants will come in every week; then participants will come in at month 2 and month 3. After the month 3 visit, visits will occur about every three months. At most visits, blood will be drawn and participants will meet with a study physician to review their overall diabetes management, and be monitored for any possible side-effects from the study medication.

Participants will be asked to do a longer test called a Mixed Meal Tolerance Test (MMTT) at the initial visit and at five additional visits while taking the assigned study medication. The MMTT involves drinking a special drink which has a controlled amount of carbohydrates, protein, and fat to measure residual insulin secretion. The test requires having an IV inserted into the arm and having blood samples taken from the IV over a period of 2 to 4 hours. After completing the two year period of taking the study medication, participants will be asked to return every 3-6 months for an additional 1-2 years to evaluate their ability to secrete insulin after discontinuing the study medication.

Being tested
Mycophenolate mofeteil (MMF), Daclizumab (DZB), Placebo control for Mycophenolate mofeteil (MMF), Placebo control for Daclizumab (DZB)
Keywords
immunosuppressive therapy, Type 1 Diabetes TrialNet, TrialNet, POPPII, POPPII-1
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.

  • Mycophenolate mofeteil (MMF)Drug

  • Daclizumab (DZB)Drug

  • Placebo control for Mycophenolate mofeteil (MMF)Drug

    Placebo pills taken orally

  • Placebo control for Daclizumab (DZB)Drug

    saline intravenous infusions

Study groups in NCT00100178
Study groupRoleWhat they receive
MMF and DBZExperimentalDZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and MMF given orally at dose of 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.
Receives: Drug: Mycophenolate mofeteil (MMF); Drug: Daclizumab (DZB)
MMF AloneExperimentalMMF given orally at dose of 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and saline intravenous infusions given at baseline and two weeks later.
Receives: Drug: Mycophenolate mofeteil (MMF); Drug: Placebo control for Daclizumab (DZB)
PlaceboPlacebo comparatorPlacebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
Receives: Drug: Placebo control for Mycophenolate mofeteil (MMF); Drug: Placebo control for Daclizumab (DZB)

What is being measured

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

  1. Mean Stimulated C-peptide Area Under the Curve

    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.

    Measured: 2 years

Timeline

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

  1. First posted24 Dec 2004 (estimated)
  2. Study startMay 2004
  3. Primary completionApr 2008
  4. Study completionApr 2008

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
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
126 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00100178
Sponsor's protocol ID
TN02 MMF/DZB
Other IDs
U01DK061055, UC4DK097835
Acronym
TN02
Status last verified
Apr 2020
First submitted
23 Dec 2004
Last updated
5 May 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn02-mmfdzb/?query=tn02

Publications

  • Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004 Jan;53(1):250-64. doi: 10.2337/diabetes.53.1.250.

    PubMed 14693724

  • Kaufman DB, Leventhal JR, Stuart J, Abecassis MM, Fryer JP, Stuart FP. Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in simultaneous pancreas-kidney transplantation: initial experience in 50 consecutive cases. Transplantation. 1999 Feb 27;67(4):586-93. doi: 10.1097/00007890-199902270-00017.

    PubMed 10071032

  • Feutren G, Papoz L, Assan R, Vialettes B, Karsenty G, Vexiau P, Du Rostu H, Rodier M, Sirmai J, Lallemand A, et al. Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet. 1986 Jul 19;2(8499):119-24. doi: 10.1016/s0140-6736(86)91943-4.

    PubMed 2873396

  • Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet. 1995 May 27;345(8961):1321-5.

    PubMed 7752752

  • Brazelton TR, Morris RE. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol. 1996 Oct;8(5):710-20. doi: 10.1016/s0952-7915(96)80090-2.

    PubMed 8902398

  • Gottlieb PA, Quinlan S, Krause-Steinrauf H, Greenbaum CJ, Wilson DM, Rodriguez H, Schatz DA, Moran AM, Lachin JM, Skyler JS; Type 1 Diabetes TrialNet MMF/DZB Study Group. Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes. Diabetes Care. 2010 Apr;33(4):826-32. doi: 10.2337/dc09-1349. Epub 2010 Jan 12.

    PubMed 20067954

  • Loechelt BJ, Boulware D, Green M, Baden LR, Gottlieb P, Krause-Steinrauf H, Weinberg A; Type 1 Diabetes TrialNet Daclizumab/Mycophenolic Acid Study Group. Epstein-Barr and other herpesvirus infections in patients with early onset type 1 diabetes treated with daclizumab and mycophenolate mofetil. Clin Infect Dis. 2013 Jan;56(2):248-54. doi: 10.1093/cid/cis848. Epub 2012 Oct 5.

    PubMed 23042974

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mycophenolate mofeteil (MMF) and Daclizumab (DZB) in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in 2 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 9 inclusion and 16 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 5 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 11 sites in United States, Canada. 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 16 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?

Mean Stimulated C-peptide Area Under the Curve (time frame: 2 years). 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 NCT00100178, which also lists 7 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 5 May 2020.

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