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

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ClinicalTrials.gov Identifier: NCT00100178
Recruitment Status : Completed
First Posted : December 24, 2004
Results First Posted : August 16, 2016
Last Update Posted : August 16, 2016
Sponsor:
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)
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator)
Condition Diabetes Mellitus, Type 1
Interventions Drug: Mycophenolate mofeteil (MMF)
Drug: Daclizumab (DZB)
Drug: Placebo control for Mycophenolate mofeteil (MMF)
Drug: Placebo control for Daclizumab (DZB)
Enrollment 126
Recruitment Details Thirteen Clinical Centers at academic institutions recruited and enrolled 126 subjects ages 8 to 45 years with autoimmune T1D for less than 3 months.
Pre-assignment Details Subjects were screened for evidence of autoantibodies and c-peptide >0.2 pmol on a stimulated 2 hr Mixed Meal Tolerance Test to determine eligibility for the study.The MMTT must be conducted at least 21 days from the diagnosis of diabetes and no more than one month (37 days) prior to the date of randomization.
Arm/Group Title MMF and DZB MMF Alone MMF-DZB Placebo Control
Hide Arm/Group Description DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years. 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. Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
Period Title: Overall Study
Started 41 31 [1] 42
Completed 32 21 32
Not Completed 9 10 10
Reason Not Completed
Lost to Follow-up             0             6             5
Adverse Event             2             2             1
Withdrawal by Subject             1             1             1
Physician Decision             6             1             3
[1]
12 subjects randomized to the MMF alone group were excluded from analysis due to randomization error
Arm/Group Title MMF and DZB MMF Alone MMF-DZB Placebo Control Total
Hide Arm/Group Description 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years AND DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later. 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 Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later. Total of all reporting groups
Overall Number of Baseline Participants 41 31 42 114
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 31 participants 42 participants 114 participants
18.4  (9.09) 17.1  (6.71) 18.8  (10.44) 18.2  (9.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 31 participants 42 participants 114 participants
Female
18
  43.9%
11
  35.5%
17
  40.5%
46
  40.4%
Male
23
  56.1%
20
  64.5%
25
  59.5%
68
  59.6%
1.Primary Outcome
Title Mean Stimulated C-peptide Area Under the Curve
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed a 4-hour mixed meal glucose tolerance test at the two-year visit were included in the analysis
Arm/Group Title MMF and DZB Placebo Control MMF Alone
Hide Arm/Group Description:
DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later, and 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years.
Placebo pills given daily for two years and saline intravenous infusions given at baseline and two weeks later.
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.
Overall Number of Participants Analyzed 22 20 18
Geometric Mean (95% Confidence Interval)
Unit of Measure: pmol/ml
0.28
(0.19 to 0.37)
0.27
(0.18 to 0.37)
0.25
(0.14 to 0.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF and DZB, Placebo Control
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MMF and DZB MMF Alone MMF-DZB Placebo Control
Hide Arm/Group Description 600 mg/m2 (2000 mg/day maximum) in 2-3 divided doses for 2 years and DZB given by intravenous infusion (1 mg/kg)at baseline and 2 weeks later . 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. Placebo pills given daily for two years AND saline intravenous infusions given at baseline and two weeks later.
All-Cause Mortality
MMF and DZB MMF Alone MMF-DZB Placebo Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
MMF and DZB MMF Alone MMF-DZB Placebo Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/41 (36.59%)      5/31 (16.13%)      5/42 (11.90%)    
Blood and lymphatic system disorders       
Lymphopenia  1  0/41 (0.00%)  0 1/31 (3.23%)  1 0/42 (0.00%)  0
Blood/Bone Marrow Unspecified  1  3/41 (7.32%)  3 1/31 (3.23%)  1 1/42 (2.38%)  1
Cardiac disorders       
Cardiac General - Other  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Eye disorders       
Cataract  1  1/41 (2.44%)  2 0/31 (0.00%)  0 0/42 (0.00%)  0
Ocular/Visual - Other  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Gastrointestinal disorders       
Diarrhea  1  1/41 (2.44%)  1 1/31 (3.23%)  1 0/42 (0.00%)  0
Vomiting  1  0/41 (0.00%)  0 0/31 (0.00%)  0 1/42 (2.38%)  1
Gastrointestinal- Other  1  0/41 (0.00%)  0 0/31 (0.00%)  0 1/42 (2.38%)  1
General disorders       
Secondary Malignancy Unspecified  1  0/41 (0.00%)  0 1/31 (3.23%)  1 0/42 (0.00%)  0
Hepatobiliary disorders       
Hepatobiliary/Pancreas - Other  1  0/41 (0.00%)  0 1/31 (3.23%)  1 0/42 (0.00%)  0
Infections and infestations       
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Metabolism and nutrition disorders       
Amylase  1  0/41 (0.00%)  0 1/31 (3.23%)  1 0/42 (0.00%)  0
Glucose, serum-high (hyperglycemia)  1  1/41 (2.44%)  1 1/31 (3.23%)  1 2/42 (4.76%)  2
Glucose, serum-low (hypoglycemia)  1  1/41 (2.44%)  1 0/31 (0.00%)  0 1/42 (2.38%)  1
Metabolic/Laboratory - Other  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Metabolic/Laboratory Unspecified  1  2/41 (4.88%)  2 0/31 (0.00%)  0 0/42 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Fracture  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Nervous system disorders       
Seizure  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Psychiatric disorders       
Mood alteration  1  1/41 (2.44%)  2 1/31 (3.23%)  2 0/42 (0.00%)  0
Reproductive system and breast disorders       
Sexual/Reproductive Function - Other  1  1/41 (2.44%)  1 0/31 (0.00%)  0 0/42 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MMF and DZB MMF Alone MMF-DZB Placebo Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   41/41 (100.00%)      31/31 (100.00%)      41/42 (97.62%)    
Blood and lymphatic system disorders       
Blood/Bone Marrow - Other  1  4/41 (9.76%)  5 5/31 (16.13%)  10 0/42 (0.00%)  0
Leukocytes (total WBC)  1  5/41 (12.20%)  7 4/31 (12.90%)  10 0/42 (0.00%)  0
Blood/Bone Marrow Unspecified  1  6/41 (14.63%)  9 7/31 (22.58%)  14 7/42 (16.67%)  13
Lymphatics - Other  1  4/41 (9.76%)  5 0/31 (0.00%)  0 0/42 (0.00%)  0
Lymphopenia  1  0/41 (0.00%)  0 2/31 (6.45%)  3 0/42 (0.00%)  0
Cardiac disorders       
Vasovagal episode  1  0/41 (0.00%)  0 2/31 (6.45%)  2 0/42 (0.00%)  0
Endocrine disorders       
Thyroid function, high (hyperthyroidism, thyrotoxicosis)  1  0/41 (0.00%)  0 2/31 (6.45%)  2 0/42 (0.00%)  0
Gastrointestinal disorders       
Dental: periodontal disease  1  0/41 (0.00%)  0 2/31 (6.45%)  2 0/42 (0.00%)  0
Dental: teeth  1  3/41 (7.32%)  3 4/31 (12.90%)  4 0/42 (0.00%)  0
Diarrhea  1  12/41 (29.27%)  14 5/31 (16.13%)  8 12/42 (28.57%)  13
Gastrointestinal - Other  1  0/41 (0.00%)  0 3/31 (9.68%)  3 5/42 (11.90%)  6
Nausea  1  7/41 (17.07%)  11 5/31 (16.13%)  5 6/42 (14.29%)  7
Vomiting  1  8/41 (19.51%)  11 7/31 (22.58%)  8 6/42 (14.29%)  6
General disorders       
Fatigue (asthenia, lethargy, malaise)  1  0/41 (0.00%)  0 2/31 (6.45%)  2 0/42 (0.00%)  0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  4/41 (9.76%)  4 3/31 (9.68%)  4 0/42 (0.00%)  0
Other AE Unspecified  1  5/41 (12.20%)  6 5/31 (16.13%)  11 5/42 (11.90%)  8
Pain  1  10/41 (24.39%)  11 6/31 (19.35%)  18 8/42 (19.05%)  11
Flu-like syndrome  1  0/41 (0.00%)  0 0/31 (0.00%)  0 4/42 (9.52%)  5
Immune system disorders       
Allergic reaction/hypersensitivity (including drug fever)  1  0/41 (0.00%)  0 2/31 (6.45%)  3 0/42 (0.00%)  0
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)  1  6/41 (14.63%)  7 0/31 (0.00%)  0 3/42 (7.14%)  3
Infections and infestations       
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e  1  5/41 (12.20%)  6 4/31 (12.90%)  4 5/42 (11.90%)  6
Infection - Other  1  5/41 (12.20%)  5 0/31 (0.00%)  0 0/42 (0.00%)  0
Infection with normal ANC or Grade 1 or 2 neutrophils  1  10/41 (24.39%)  18 6/31 (19.35%)  15 7/42 (16.67%)  8
Infection with unknown ANC  1  36/41 (87.80%)  106 27/31 (87.10%)  61 34/42 (80.95%)  94
Infection Unspecified  1  10/41 (24.39%)  23 2/31 (6.45%)  11 6/42 (14.29%)  8
Metabolism and nutrition disorders       
Glucose, serum-high (hyperglycemia)  1  0/41 (0.00%)  0 3/31 (9.68%)  5 0/42 (0.00%)  0
Glucose, serum-low (hypoglycemia)  1  13/41 (31.71%)  24 9/31 (29.03%)  21 10/42 (23.81%)  26
Metabolic/Laboratory Unspecified  1  8/41 (19.51%)  10 0/31 (0.00%)  0 0/42 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Fracture  1  3/41 (7.32%)  3 0/31 (0.00%)  0 7/42 (16.67%)  8
Musculoskeletal/Soft Tissue - Other  1  8/41 (19.51%)  13 3/31 (9.68%)  5 9/42 (21.43%)  10
Nervous system disorders       
Dizziness  1  0/41 (0.00%)  0 2/31 (6.45%)  2 0/42 (0.00%)  0
Psychiatric disorders       
Mood alteration  1  0/41 (0.00%)  0 2/31 (6.45%)  2 3/42 (7.14%)  3
Reproductive system and breast disorders       
Irregular menses (change from baseline)  1  3/41 (7.32%)  4 0/31 (0.00%)  0 0/42 (0.00%)  0
Sexual/Reproductive Function - Other  1  0/41 (0.00%)  0 0/31 (0.00%)  0 3/42 (7.14%)  3
Respiratory, thoracic and mediastinal disorders       
Cough  1  11/41 (26.83%)  14 2/31 (6.45%)  2 4/42 (9.52%)  5
Skin and subcutaneous tissue disorders       
Dermatology/Skin - Other  1  4/41 (9.76%)  5 6/31 (19.35%)  7 0/42 (0.00%)  0
Rash/desquamation  1  11/41 (26.83%)  14 3/31 (9.68%)  5 5/42 (11.90%)  6
Rash: acne/acneiform  1  3/41 (7.32%)  4 4/31 (12.90%)  4 0/42 (0.00%)  0
Vascular disorders       
Hemorrhage, pulmonary/upper respiratory  1  0/41 (0.00%)  0 3/31 (9.68%)  5 0/42 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Peter Gottleib, MD
Organization: Barbara Davis Center for Childhood Diabetes, Health Sciences Center, University of Colorado
Phone: 303-724-6714
EMail: Peter.Gottleib@uchsc.edu
Layout table for additonal information
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00100178     History of Changes
Other Study ID Numbers: MMFDZB (IND) (completed)
First Submitted: December 23, 2004
First Posted: December 24, 2004
Results First Submitted: May 13, 2016
Results First Posted: August 16, 2016
Last Update Posted: August 16, 2016