Study of Antithymocyte Globulin for Treatment of New-onset T1DM (START)

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00515099
First received: August 10, 2007
Last updated: March 25, 2014
Last verified: March 2014
Results First Received: February 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: New-onset Type 1 Diabetes Mellitus
Interventions: Drug: Antithymocyte globulin
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study planned a 30-month subject enrollment (e.g. accrual) period which was extended to 40-months in an effort to achieve the planned sample size. Subject enrollment closed on June 30, 2011 after 88% of the targeted number of study participants was enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects ages 12 to 35 years who were first diagnosed with type 1 diabetes mellitus (T1DM) within 100 days of enrollment.

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.

Participant Flow:   Overall Study
    Antithymocyte Globulin     Placebo  
STARTED     38     20  
COMPLETED     36     19  
NOT COMPLETED     2     1  
Lost to Follow-up                 0                 1  
Withdrawal by Subject                 1                 0  
IRB Recommendation                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.
Total Total of all reporting groups

Baseline Measures
    Antithymocyte Globulin     Placebo     Total  
Number of Participants  
[units: participants]
  38     20     58  
Age  
[units: years]
Mean ± Standard Deviation
  19.4  ± 6.6     20.5  ± 7.1     19.8  ± 6.7  
Age, Customized  
[units: participants]
     
12-17 Years     19     10     29  
18-35 Years     19     10     29  
Gender  
[units: participants]
     
Female     14     9     23  
Male     24     11     35  
Region of Enrollment  
[units: participants]
     
United States     38     20     58  



  Outcome Measures

1.  Primary:   2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)   [ Time Frame: Baseline (Pre-treatment initiation), Month 12 ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
Measure Description C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.
Time Frame Baseline (Pre-treatment initiation), Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat

Reporting Groups
  Description
Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg
Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg.

Measured Values
    Antithymocyte Globulin     Placebo  
Number of Participants Analyzed  
[units: participants]
  38     20  
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)  
[units: pmol/mL]
Mean ± Standard Deviation
   
Baseline (Pre-treatment initiation)     0.86  ± 0.37     0.93  ± 0.50  
Month 12     0.66  ± 0.37     0.69  ± 0.52  
Change from Baseline (Pre-treatment initiation)     -0.20  ± 0.29     -0.24  ± 0.26  


Statistical Analysis 1 for 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.60
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Primary imputation method used for missing Month 12 AUC. Measuring range for C-peptide is 0.05-30 ng/mL
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is for testing treatment effect using an analysis of covariance with baseline ln(AUC+1) as a covariate and change in ln(AUC+1) from baseline as the outcome variable.



2.  Secondary:   4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)   [ Time Frame: Baseline (Pre-treatment initiation), Month 12 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   Insulin Use in Units Per Kilogram Body Weight Per Day   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Proportion of Subjects Who Are Exogenous-Insulin-Free   [ Time Frame: Months 12, 18, and 24; possibly up to 60 months ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Major Hypoglycemic Events Occurring Since Treatment Randomization   [ Time Frame: Baseline through Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

6.  Secondary:   2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT)   [ Time Frame: Month 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Hemoglobin A1c   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Changes in Mean C-peptide Area Under the Curve ( AUC ) Results in Response to Standardized 2-hour and 4- Hour MMTTs Over Time   [ Time Frame: Months 12 and 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Enrollment for this trial was closed at 58 participants and did not meet the planned sample size of 66 participants due to slow accrual.


  More Information
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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: Associate Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00515099     History of Changes
Other Study ID Numbers: DAIT ITN028AI
Study First Received: August 10, 2007
Results First Received: February 10, 2014
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board