Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Rituximab in New Onset Type 1 Diabetes

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 : November 2, 2016
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Diabetes Association
Juvenile Diabetes Research Foundation
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: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Anti-CD20 (rituximab)
Drug: Placebo Comparator
Enrollment 87
Recruitment Details Participants with newly diagnosed type 1 diabetes recruited from 12 TrialNet Clinical Centers between
Pre-assignment Details 126 patients were assessed; 39 were excluded; 87 underwent randomization (57 were assigned to receive rituximab and 30 were assigned to receive placebo)
Arm/Group Title Rituximab Treatment Placebo
Hide Arm/Group Description Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
Period Title: Overall Study
Started 57 30
Completed 49 29
Not Completed 8 1
Reason Not Completed
Pregnancy             1             0
Withdrawal by Subject             2             0
Dificulting establishing IV             1             0
FDA Safety Alert             4             1
Arm/Group Title Rituximab Treatment Placebo Total
Hide Arm/Group Description Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study Placebo infusions were given to participants in control group on days 1, 8, 15, and 22. Total of all reporting groups
Overall Number of Baseline Participants 57 30 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants 30 participants 87 participants
19.0  (8.6) 17.4  (8.0) 18.5  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants 30 participants 87 participants
Female
21
  36.8%
12
  40.0%
33
  37.9%
Male
36
  63.2%
18
  60.0%
54
  62.1%
1.Primary Outcome
Title 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
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.

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.

Time Frame When all participants complete the 1 year visit
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rituximab Treatment Placebo
Hide Arm/Group Description:
Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study
Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
Overall Number of Participants Analyzed 49 29
Mean (95% Confidence Interval)
Unit of Measure: pmol per mL
0.58
(0.476 to 0.691)
0.429
(0.289 to 0.585)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab Treatment, Placebo
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 0.05
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.139
Confidence Interval (2-Sided) 95%
-0.0699 to 0.348
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.104
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rituximab Treatment Placebo
Hide Arm/Group Description Four intravenous infusions (375 mg per square meter of body-surface area) were given on days 1, 8, 15, and 22 of the study Placebo infusions were given to participants in control group on days 1, 8, 15, and 22.
All-Cause Mortality
Rituximab Treatment Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/57 (19.30%)      9/30 (30.00%)    
Blood and lymphatic system disorders     
Neutrophils/granulocytes (ANC/AGC)  1  4/57 (7.02%)  4 1/30 (3.33%)  2
Endocrine disorders     
Endocrine- other  1  2/57 (3.51%)  2 2/30 (6.67%)  3
Pancreatic endocrine: glucose intolerance  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Gastrointestinal disorders     
Gastrointestinal Other  1  1/57 (1.75%)  1 0/30 (0.00%)  0
General disorders     
Sudden Death  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Immune system disorders     
Allergic reaction/hypersensitivity (including drug fever)  1  1/57 (1.75%)  1 0/30 (0.00%)  0
Infections and infestations     
Infection Other  1  0/57 (0.00%)  0 2/30 (6.67%)  2
Infection with unknown ANC- pneumonia  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Infection with unknown ANC- Sinus  1  1/57 (1.75%)  1 0/30 (0.00%)  0
Metabolism and nutrition disorders     
Acidosis (metabolic or respiratory)  1  1/57 (1.75%)  1 1/30 (3.33%)  3
Glucose, serum-high (hyperglycemia)  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Glucose, serum-low (hypoglycemia)  1  1/57 (1.75%)  1 0/30 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Fracture  1  1/57 (1.75%)  1 0/30 (0.00%)  0
Renal and urinary disorders     
Renal failure  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary/Upper Respiratory - Other  1  0/57 (0.00%)  0 1/30 (3.33%)  1
Skin and subcutaneous tissue disorders     
Dermatology/Skin Other  1  1/57 (1.75%)  1 0/30 (0.00%)  0
Surgical and medical procedures     
Intra-operative Injury - Other  1  0/57 (0.00%)  0 1/30 (3.33%)  1
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%
Rituximab Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   56/57 (98.25%)      29/30 (96.67%)    
Blood and lymphatic system disorders     
Blood/Bone Marrow - Other  1  0/57 (0.00%)  0 3/30 (10.00%)  9
Leukocytes (total WBC)  1  7/57 (12.28%)  12 2/30 (6.67%)  3
Lymphopenia  1  5/57 (8.77%)  7 2/30 (6.67%)  2
Neutrophils/granulocytes (ANC/AGC)  1  11/57 (19.30%)  18 9/30 (30.00%)  14
Cardiac disorders     
Supraventricular and nodal arrhythmia  1  12/57 (21.05%)  13 0/30 (0.00%)  0
Vasovagal episode  1  3/57 (5.26%)  5 2/30 (6.67%)  2
Hypertension  1  6/57 (10.53%)  6 0/30 (0.00%)  0
Hypotension  1  18/57 (31.58%)  25 5/30 (16.67%)  9
Endocrine disorders     
Endocrine - Other  1  0/57 (0.00%)  0 5/30 (16.67%)  5
Gastrointestinal disorders     
Dental: teeth  1  5/57 (8.77%)  5 0/30 (0.00%)  0
Diarrhea  1  12/57 (21.05%)  15 3/30 (10.00%)  5
Gastrointestinal - Other  1  4/57 (7.02%)  4 5/30 (16.67%)  6
Nausea  1  25/57 (43.86%)  26 2/30 (6.67%)  2
Vomiting  1  16/57 (28.07%)  19 3/30 (10.00%)  3
General disorders     
Constitutional Symptoms - Other  1  3/57 (5.26%)  3 2/30 (6.67%)  3
Fatigue (asthenia, lethargy, malaise)  1  6/57 (10.53%)  8 2/30 (6.67%)  2
Fever  1  17/57 (29.82%)  19 5/30 (16.67%)  7
Rigors/chills  1  3/57 (5.26%)  3 0/30 (0.00%)  0
Sinus Pain  1  13/57 (22.81%)  22 7/30 (23.33%)  13
Other AE  1  5/57 (8.77%)  7 4/30 (13.33%)  6
Flu-like syndrome  1  4/57 (7.02%)  5 2/30 (6.67%)  2
Immune system disorders     
Allergic rhinitis  1  10/57 (17.54%)  11 3/30 (10.00%)  5
Infections and infestations     
Infection - Other  1  14/57 (24.56%)  15 2/30 (6.67%)  2
Pelvis Infection with normal ANC or Grade 1 or 2 neutrophils  1  3/57 (5.26%)  3 2/30 (6.67%)  2
Skin Infection with normal ANC or Grade 1 or 2 neutrophils  1  4/57 (7.02%)  4 2/30 (6.67%)  2
Pharynx Infection with unknown ANC  1  8/57 (14.04%)  14 4/30 (13.33%)  8
Sinus Infection with unknown ANC  1  3/57 (5.26%)  3 2/30 (6.67%)  6
Upper Airway Infection with unknown ANC  1  14/57 (24.56%)  25 12/30 (40.00%)  22
Metabolism and nutrition disorders     
Glucose, serum-low (hypoglycemia)  1  5/57 (8.77%)  5 4/30 (13.33%)  4
Musculoskeletal and connective tissue disorders     
Fracture  1  7/57 (12.28%)  9 4/30 (13.33%)  4
Musculoskeletal/Soft Tissue - Other  1  12/57 (21.05%)  15 7/30 (23.33%)  11
Nervous system disorders     
Dizziness  1  3/57 (5.26%)  3 0/30 (0.00%)  0
Neurology - Other  1  3/57 (5.26%)  4 0/30 (0.00%)  0
Reproductive system and breast disorders     
Sexual/Reproductive Function - Other  1  3/57 (5.26%)  4 0/30 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchospasm, wheezing  1  0/57 (0.00%)  0 2/30 (6.67%)  4
Cough  1  8/57 (14.04%)  10 4/30 (13.33%)  4
Dyspnea (shortness of breath)  1  4/57 (7.02%)  5 0/30 (0.00%)  0
Edema, larynx  1  6/57 (10.53%)  7 0/30 (0.00%)  0
Pulmonary/Upper Respiratory - Other  1  3/57 (5.26%)  4 2/30 (6.67%)  2
Skin and subcutaneous tissue disorders     
Dermatology/Skin - Other  1  6/57 (10.53%)  9 6/30 (20.00%)  7
Pruritus/itching  1  21/57 (36.84%)  22 0/30 (0.00%)  0
Rash/desquamation  1  24/57 (42.11%)  26 3/30 (10.00%)  4
Vascular disorders     
Vascular - Other  1  3/57 (5.26%)  5 0/30 (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
Name/Title: Carla Greenbaum, MD
Organization: Type 1 Diabetes TrialNet
Publications:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00279305     History of Changes
Other Study ID Numbers: Ritux (IND) (completed)
First Submitted: January 17, 2006
First Posted: January 19, 2006
Results First Submitted: May 12, 2016
Results First Posted: August 18, 2016
Last Update Posted: November 2, 2016