Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes (START)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by National Institute of Allergy and Infectious Diseases (NIAID).
Recruitment status was  Active, not recruiting
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: January 8, 2013
Last verified: January 2012

August 10, 2007
January 8, 2013
August 2007
June 2012   (final data collection date for primary outcome measure)
2-hour C-peptide AUC in response to MMTT [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
2-hour C-peptide AUC in response to MMTT [ Time Frame: Month 12 ]
Complete list of historical versions of study NCT00515099 on ClinicalTrials.gov Archive Site
  • 4-hour C-peptide AUC in response to MMTT [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Insulin use in units per kilogram body weight per day [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects who are exogenous-insulin-free [ Time Frame: Months 12, 18, and 24, possibly up to 60 months ] [ Designated as safety issue: No ]
  • Major hypoglycemic events occurring since randomization [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: Yes ]
  • 2-hour and 4-hour C-peptide AUC in response to an MMTT [ Time Frame: Months 24 ] [ Designated as safety issue: No ]
  • HbA1C levels [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
  • Changes of C-peptide AUC (2 and 4 hours) over time [ Time Frame: Months 12 and 24 ] [ Designated as safety issue: No ]
  • Frequency and severity of all adverse events in participants receiving Thymoglobulin or placebo [ Time Frame: Day 1 to 24 months; possibly up to 60 months ] [ Designated as safety issue: Yes ]
  • The rate adverse events in participants receiving Thymoglobulin [ Time Frame: Day 1 to 24 months; possibly up to 60 months ] [ Designated as safety issue: Yes ]
    The adverse events include: Infusion reactions, cytokine release syndrome, opportunistic infections, lymphopenia, CD4/CD8 ratio, neutropenia, thrombocytopenia, serum sickness.
  • 4-hour C-peptide AUC in response to MMTT [ Time Frame: Month 12 ]
  • Insulin use in units per kilogram body weight per day [ Time Frame: Months 12 and 24 ]
  • Proportion of subjects who are exogenous-insulin-free [ Time Frame: Months 12, 18, and 24, possibly up to 60 months ]
  • Hypoglycemic events occurring since randomization [ Time Frame: months 12 and 24 ]
  • 2-hour and 4-hour C-peptide AUC in response to an MMTT [ Time Frame: Months 12 and 24 ]
  • HbA1C levels [ Time Frame: Months 12 and 24 ]
  • Changes of C-peptide AUC (2 and 4 hours) over time [ Time Frame: Months 12 and 24 ]
  • Safety (adverse events frequency, severity)
Not Provided
Not Provided
 
Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes
Effect of Antithymocyte Globulin on Preserving Beta Cell Function in New Onset Type 1 Diabetes Mellitus

Thymoglobulin is an antibody preparation that is commonly used to treat and prevent organ transplant rejection. The START trial aims to determine whether Thymoglobulin treatment can halt the progression of newly diagnosed type 1 diabetes when given within 12 weeks of disease diagnosis.

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain proper blood glucose levels in response to daily activities, such as eating or exercise. Generally, at the time someone is diagnosed with type 1 diabetes, not all of a person's beta cells have been destroyed - between 15-40% remain healthy and are still able to produce insulin. Importantly, even small amounts of naturally produced insulin can improve blood sugar control, make daily management of diabetes less complicated, and reduce the risk of long term complications. Preserving the remaining precious beta cells is therefore the goal of the START trial.

The medication being tested in the START trial is called Thymoglobulin®, a mixture of specialized proteins called antibodies. Thymoglobulin attaches itself to white blood cells known as T cells, some of which are responsible for the immune system's attack on beta cells that occurs in type 1 diabetes. Thymoglobulin can change how T cells work, and can eliminate a large proportion of the T cells from the bloodstream temporarily. Treatment of new onset type 1 diabetes with Thymoglobulin is therefore expected to alter the behavior of the T cells to halt their attack, and also reduce T cell numbers, so that new T cells that grow in their place will learn to accept the beta cells, rather than attacking them.

Following an initial screening appointment, eligible participants will be randomly assigned to one of two groups: Group 1 will receive the study treatment while Group 2 is a control group that will receive a placebo. Each participant has a 2 in 3 chance of being assigned to the treatment group, and a 1 in 3 chance of being assigned to the placebo. The START trial is a blinded study, so neither participants nor study physicians will know to which group an individual has been assigned. All participants will receive intensive diabetes management. Participants in both groups will be admitted to the hospital for 5-8 days to receive infusions of either the study drug or placebo.

The duration of the study is 2 years. Participants will have 8 follow-up appointments in the first year and 4 visits in the second year. Most of these visits will last 1- 2 hours. A review of interval health, a physical exam, an assessment of diabetes control including recent 5 day insulin use and blood sugar testing, and blood collection for laboratory testing will occur at each visit. Four of the visits will last about 5 hours, during which participants will undergo mixed-meal tolerance testing. This involves drinking a special drink, similar to a milkshake, and having blood specimens taken over a 4-hour period.

Subjects will be reimbursed for travel and parking expenses, and will receive compensation for their participation in the longer mixed meal tolerance test visits.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Diabetes Mellitus, Type 1
  • Drug: Antithymocyte globulin
    Daily 4-day escalating dose
    Other Name: Thymoglobulin
  • Drug: Placebo
    Daily 4-day saline solution
  • Experimental: Thymoglobulin
    Intervention: Drug: Antithymocyte globulin
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
58
June 2013
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of type 1 diabetes (according to American Diabetes Association [ADA] criteria) within the 100 days of enrollment.
  • Positive for one or more autoantibodies (anti-glutamic acid decarboxylase [GAD], anti-insulin, or IA-2 autoantibodies)
  • Peak stimulated C-peptide level >0.4 pmol/mL or >1.2ng/mL following an MMTT
  • Serologic evidence of prior EBV infection
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • Any sign of active infection (e.g., hepatitis, tuberculosis, EBV, CMV, or toxoplasmosis) at screening
  • Positive for HIV, tuberculosis, or hepatitis B at screening
  • Prior history of any significant cardiac disease, such as congestive heart failure, arrhythmia, or structural defects, or suspicion thereof
  • Use of glucocorticoids in the 28 days prior to study entry; or topical use of glucocorticoids
  • Use of diabetes medications (other than insulin) that may affect glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, or amylin
  • Evidence of liver dysfunction
  • Evidence of kidney disease
  • Pregnancy or plan to become pregnant
  • Leukopenia (<3,000 leukocytes/µL), neutropenia (<1,500neutrophils/µL), lymphopenia (<800 lymphocytes/µL), or thrombocytopenia (<125,000 platelets/µL).
  • Prior treatment with rabbit ATG or known hypersensitivity or exposure to rabbit sera-derived products.
  • Vaccination with a live virus within the last 6 weeks before enrollment.
  • Prior or current therapy that is known to cause a significant, ongoing change in the course of T1DM or immunologic status.
  • Any condition that may compromise study participation or may confound the interpretation of the study results.
Both
12 Years to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00515099
DAIT ITN028AI
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Principal Investigator: Stephen Gitelman, MD University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP