Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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: October 24, 2016
Last verified: October 2016
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
Subjects were recruited during an approximate 40-month accrual period. Initially 66 subjects were planned, however enrollment closed early at 58 subjects on June 30, 2011 secondary to slow accrual (planned 30-month accrual period).

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   35   16 
NOT COMPLETED   3   4 
Lost to Follow-up                0                4 
Withdrawal by Subject                2                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 
Overall Participants Analyzed 
[Units: Participants]
 38   20   58 
Age 
[Units: Participants]
     
<=18 years   19   10   29 
Between 18 and 65 years   19   10   29 
>=65 years   0   0   0 
Age 
[Units: Years]
Mean (Standard Deviation)
 19.4  (6.6)   20.5  (7.1)   19.8  (6.7) 
Age, Customized 
[Units: Participants]
     
12 -15 Years   13   6   19 
16 - 21 Years   13   6   19 
22 - 35 Years   12   8   20 
Gender 
[Units: Participants]
     
Female   14   9   23 
Male   24   11   35 
Region of Enrollment 
[Units: Participants]
     
United States   38   20   58 


  Outcome Measures
  Show All 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 ]

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 ]

3.  Secondary:   Insulin Use in Units Per Kilogram Body Weight Per Day   [ Time Frame: Baseline (Pre-treatment), Months 12 and 24 ]

4.  Secondary:   Number of Participants Who Are Exogenous-Insulin-Free   [ Time Frame: Baseline (Pre-treatment), Months 12 , 18, and 24 ]

5.  Secondary:   Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation   [ Time Frame: Baseline (Pre-treatment), Months 12 , and 24 ]

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: Baseline (Pre-treatment), Month 24 ]

7.  Secondary:   Hemoglobin A1c   [ Time Frame: Baseline (Pre-treatment), Months 12 and 24 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame From baseline (e.g., when informed consent signed) through study completion. The first participant enrolled in September 2007 and the last participant last visit for the study occurred in July 2013.
Additional Description

Adverse Events (AEs) could be discovered through any of these methods:

  • Observing the participant.
  • Questioning the participant in an objective manner.
  • Receiving an unsolicited complaint from the participant.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other Adverse Events
    Antithymocyte Globulin   Placebo
Total, other (not including serious) adverse events     
# participants affected / at risk   38/38 (100.00%)   20/20 (100.00%) 
Blood and lymphatic system disorders     
Leukopenia † 1     
# participants affected / at risk   14/38 (36.84%)   0/20 (0.00%) 
# events   20   0 
Lymphadenopathy † 1     
# participants affected / at risk   1/38 (2.63%)   2/20 (10.00%) 
# events   1   2 
Lymphopenia † 1     
# participants affected / at risk   38/38 (100.00%)   0/20 (0.00%) 
# events   48   0 
Neutropenia † 1     
# participants affected / at risk   9/38 (23.68%)   2/20 (10.00%) 
# events   10   4 
Thrombocytopenia † 1     
# participants affected / at risk   5/38 (13.16%)   0/20 (0.00%) 
# events   5   0 
Cardiac disorders     
Bradycardia † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Ear and labyrinth disorders     
Ear pain † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Middle ear effusion † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   2 
Eye disorders     
Eye irritation † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Ocular hyperaemia † 1     
# participants affected / at risk   3/38 (7.89%)   0/20 (0.00%) 
# events   3   0 
Visual impairment † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   3/38 (7.89%)   1/20 (5.00%) 
# events   3   1 
Abdominal pain lower † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Abdominal pain upper † 1     
# participants affected / at risk   3/38 (7.89%)   1/20 (5.00%) 
# events   3   1 
Constipation † 1     
# participants affected / at risk   5/38 (13.16%)   0/20 (0.00%) 
# events   6   0 
Diarrhoea † 1     
# participants affected / at risk   5/38 (13.16%)   3/20 (15.00%) 
# events   5   3 
Dyspepsia † 1     
# participants affected / at risk   2/38 (5.26%)   3/20 (15.00%) 
# events   2   3 
Gastritis † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Gastrooesophageal reflux disease † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Nausea † 1     
# participants affected / at risk   7/38 (18.42%)   5/20 (25.00%) 
# events   8   7 
Oral disorder † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   4   0 
Toothache † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Vomiting † 1     
# participants affected / at risk   3/38 (7.89%)   3/20 (15.00%) 
# events   4   3 
General disorders     
Catheter site pain † 1     
# participants affected / at risk   5/38 (13.16%)   1/20 (5.00%) 
# events   5   1 
Chest discomfort † 1     
# participants affected / at risk   3/38 (7.89%)   1/20 (5.00%) 
# events   3   1 
Chest pain † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   2   1 
Face oedema † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Fatigue † 1     
# participants affected / at risk   3/38 (7.89%)   4/20 (20.00%) 
# events   4   5 
Influenza like illness † 1     
# participants affected / at risk   2/38 (5.26%)   3/20 (15.00%) 
# events   2   3 
Infusion site pain † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Infusion site swelling † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Injection site discolouration † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Injection site hypertrophy † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Malaise † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   2   1 
Pain † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   2   1 
Pyrexia † 1     
# participants affected / at risk   6/38 (15.79%)   1/20 (5.00%) 
# events   6   1 
Hepatobiliary disorders     
Hyperbilirubinaemia † 1     
# participants affected / at risk   3/38 (7.89%)   0/20 (0.00%) 
# events   3   0 
Immune system disorders     
Cytokine release syndrome † 1     
# participants affected / at risk   36/38 (94.74%)   1/20 (5.00%) 
# events   36   1 
Seasonal allergy † 1     
# participants affected / at risk   7/38 (18.42%)   2/20 (10.00%) 
# events   8   2 
Serum sickness † 1     
# participants affected / at risk   36/38 (94.74%)   0/20 (0.00%) 
# events   37   0 
Infections and infestations     
Bronchitis † 1     
# participants affected / at risk   4/38 (10.53%)   0/20 (0.00%) 
# events   5   0 
Ear infection † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Eye infection † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   2 
Gastroenteritis † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   2   1 
Gingival infection † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Influenza † 1     
# participants affected / at risk   3/38 (7.89%)   0/20 (0.00%) 
# events   3   0 
Nasopharyngitis † 1     
# participants affected / at risk   5/38 (13.16%)   1/20 (5.00%) 
# events   5   1 
Oral herpes † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Otitis media † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Pharyngitis † 1     
# participants affected / at risk   2/38 (5.26%)   2/20 (10.00%) 
# events   2   2 
Pharyngitis streptococcal † 1     
# participants affected / at risk   2/38 (5.26%)   2/20 (10.00%) 
# events   3   2 
Pneumonia † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Sinusitis † 1     
# participants affected / at risk   5/38 (13.16%)   1/20 (5.00%) 
# events   7   1 
Upper respiratory tract infection † 1     
# participants affected / at risk   16/38 (42.11%)   7/20 (35.00%) 
# events   32   16 
Viral infection † 1     
# participants affected / at risk   5/38 (13.16%)   3/20 (15.00%) 
# events   10   3 
Injury, poisoning and procedural complications     
Arthropod bite † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Contusion † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Excoriation † 1     
# participants affected / at risk   4/38 (10.53%)   0/20 (0.00%) 
# events   5   0 
Fibula fracture † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Foot fracture † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Hand fracture † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Joint sprain † 1     
# participants affected / at risk   3/38 (7.89%)   0/20 (0.00%) 
# events   3   0 
Sunburn † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   3   1 
Investigations     
Alanine aminotransferase increased † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   3   0 
Aspartate aminotransferase increased † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   4   0 
CD4 lymphocytes decreased † 1     
# participants affected / at risk   37/38 (97.37%)   0/20 (0.00%) 
# events   37   0 
Glycosylated haemoglobin increased † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Haptoglobin increased † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
T-lymphocyte count decreased † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Weight decreased † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Metabolism and nutrition disorders     
Hyperglycaemia † 1     
# participants affected / at risk   7/38 (18.42%)   1/20 (5.00%) 
# events   8   3 
Hypoglycaemia † 1     
# participants affected / at risk   31/38 (81.58%)   16/20 (80.00%) 
# events   493   201 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   4/38 (10.53%)   3/20 (15.00%) 
# events   4   4 
Back pain † 1     
# participants affected / at risk   4/38 (10.53%)   5/20 (25.00%) 
# events   5   6 
Muscle spasms † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   2   1 
Musculoskeletal pain † 1     
# participants affected / at risk   1/38 (2.63%)   3/20 (15.00%) 
# events   1   3 
Myalgia † 1     
# participants affected / at risk   4/38 (10.53%)   2/20 (10.00%) 
# events   4   3 
Pain in extremity † 1     
# participants affected / at risk   2/38 (5.26%)   2/20 (10.00%) 
# events   3   2 
Rotator cuff syndrome † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   4/38 (10.53%)   2/20 (10.00%) 
# events   4   2 
Dysaesthesia † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Headache † 1     
# participants affected / at risk   18/38 (47.37%)   10/20 (50.00%) 
# events   25   15 
Lethargy † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Migraine † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Somnolence † 1     
# participants affected / at risk   0/38 (0.00%)   2/20 (10.00%) 
# events   0   3 
Pregnancy, puerperium and perinatal conditions     
Pregnancy † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Psychiatric disorders     
Affective disorder † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Agitation † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Anxiety † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Attention deficit/hyperactivity disorder † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Depression † 1     
# participants affected / at risk   3/38 (7.89%)   3/20 (15.00%) 
# events   3   3 
Insomnia † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Restlessness † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Renal and urinary disorders     
Proteinuria † 1     
# participants affected / at risk   0/38 (0.00%)   2/20 (10.00%) 
# events   0   2 
Reproductive system and breast disorders     
Dysmenorrhoea † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Ovarian cyst † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   3   0 
Respiratory, thoracic and mediastinal disorders     
Asthma † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Bronchospasm † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Cough † 1     
# participants affected / at risk   8/38 (21.05%)   4/20 (20.00%) 
# events   10   5 
Epistaxis † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Nasal congestion † 1     
# participants affected / at risk   3/38 (7.89%)   3/20 (15.00%) 
# events   4   4 
Oropharyngeal pain † 1     
# participants affected / at risk   9/38 (23.68%)   5/20 (25.00%) 
# events   13   6 
Pharyngeal erythema † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Productive cough † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Rhinitis allergic † 1     
# participants affected / at risk   2/38 (5.26%)   1/20 (5.00%) 
# events   4   1 
Rhinorrhoea † 1     
# participants affected / at risk   1/38 (2.63%)   3/20 (15.00%) 
# events   1   3 
Sinus congestion † 1     
# participants affected / at risk   4/38 (10.53%)   1/20 (5.00%) 
# events   4   1 
Tonsillar hypertrophy † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Skin and subcutaneous tissue disorders     
Acne † 1     
# participants affected / at risk   7/38 (18.42%)   1/20 (5.00%) 
# events   8   1 
Blister † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Dermatitis contact † 1     
# participants affected / at risk   2/38 (5.26%)   3/20 (15.00%) 
# events   2   3 
Eczema † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   1 
Ingrowing nail † 1     
# participants affected / at risk   2/38 (5.26%)   0/20 (0.00%) 
# events   2   0 
Lipoatrophy † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   2 
Lipohypertrophy † 1     
# participants affected / at risk   0/38 (0.00%)   2/20 (10.00%) 
# events   0   4 
Pruritus † 1     
# participants affected / at risk   4/38 (10.53%)   3/20 (15.00%) 
# events   4   4 
Rash † 1     
# participants affected / at risk   7/38 (18.42%)   2/20 (10.00%) 
# events   8   3 
Rash papular † 1     
# participants affected / at risk   3/38 (7.89%)   0/20 (0.00%) 
# events   3   0 
Rash pruritic † 1     
# participants affected / at risk   1/38 (2.63%)   1/20 (5.00%) 
# events   1   5 
Urticaria † 1     
# participants affected / at risk   2/38 (5.26%)   2/20 (10.00%) 
# events   2   2 
Vascular disorders     
Flushing † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Hot flush † 1     
# participants affected / at risk   0/38 (0.00%)   1/20 (5.00%) 
# events   0   1 
Hypotension † 1     
# participants affected / at risk   0/38 (0.00%)   3/20 (15.00%) 
# events   0   3 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.1



  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.


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


Publications of Results:
Other 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: October 24, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board