Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes (START)
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.
Diabetes Mellitus, Type 1
Drug: Antithymocyte globulin
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Effect of Antithymocyte Globulin on Preserving Beta Cell Function in New Onset Type 1 Diabetes Mellitus|
- 2-hour C-peptide AUC in response to MMTT [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
- 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.
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||June 2013|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Drug: Antithymocyte globulin
Daily 4-day escalating dose
Other Name: Thymoglobulin
|Placebo Comparator: Placebo||
Daily 4-day saline solution
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.
|United States, California|
|Children's Hospital/USC School of Medicine|
|Los Angeles, California, United States, 90027|
|Children's Hospital and Research Center|
|Oakland, California, United States, 92609|
|UCSD/San Diego Children's Hospital|
|San Diego, California, United States, 92123|
|Diabetes Center at UCSF|
|San Francisco, California, United States, 94143|
|United States, Colorado|
|Barbara Davis Center for Childhood Diabetes, University of Colorado|
|Aurora, Colorado, United States, 80010|
|United States, Georgia|
|Emory Children's Center|
|Atlanta, Georgia, United States, 30322|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Children's Mercy Hospital|
|Kansas City, Missouri, United States, 64108|
|United States, Pennsylvania|
|University of Pennsylvania/Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Stephen Gitelman, MD||University of California, San Francisco|