New Onset of Type 1 Diabetes Mycophenolate Mofetil-Daclizumab Clinical Trial (TN02)

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

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.)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

126

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles
      • San Francisco, California, United States, 94143
        • University of California-San Francisco
      • Stanford, California, United States, 94305-5208
        • Stanford University
    • Colorado
      • Denver, Colorado, United States, 80262
        • Barbara Davis Center for Childhood Diabetes, University of Colorado
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Columbia University
    • 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

4 years to 41 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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.]

  • 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.

Exclusion Criteria:

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.
  • 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.

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MMF and DBZ
DZB 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.
Drug: Mycophenolate mofeteil (MMF)
Drug: Daclizumab (DZB)
Experimental: MMF Alone
MMF 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.
Drug: Mycophenolate mofeteil (MMF)
Drug: Placebo control for Daclizumab (DZB)
saline intravenous infusions
Placebo Comparator: Placebo
Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
Drug: Placebo control for Daclizumab (DZB)
saline intravenous infusions
Drug: Placebo control for Mycophenolate mofeteil (MMF)
Placebo pills taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Stimulated C-peptide Area Under the Curve
Time Frame: 2 years
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.
2 years

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
National Center for Research Resources (NCRR)

Investigators

  • Study Chair: Jay S Skyler, M.D., University of Miami

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

May 1, 2004

Primary Completion (Actual)

April 1, 2008

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

December 23, 2004

First Submitted That Met QC Criteria

December 23, 2004

First Posted (Estimate)

December 24, 2004

Study Record Updates

Last Update Posted (Actual)

May 5, 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

  • TN02 MMF/DZB
  • UC4DK097835 (U.S. NIH Grant/Contract)
  • 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/tn02-mmfdzb/?query=tn02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on Diabetes Mellitus, Type 1

Clinical Trials on Mycophenolate mofeteil (MMF)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe