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Study of Antithymocyte Globulin for Treatment of New-onset T1DM

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: New-onset Type 1 Diabetes Mellitus

Intervention: Antithymocyte globulin (Drug); Placebo (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Stephen Gitelman, MD, Principal Investigator, Affiliation: University of California, San Francisco

Summary

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

Clinical Details

Official title: Effect of Antithymocyte Globulin on Preserving Beta Cell Function in New Onset Type 1 Diabetes Mellitus

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Primary outcome: 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)

Secondary outcome:

4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)

Insulin Use in Units Per Kilogram Body Weight Per Day

Number of Participants Who Are Exogenous-Insulin-Free

Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation

2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT)

Hemoglobin A1c

Detailed description: Type 1 diabetes mellitus (T1DM) 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 T1DM, 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 antithymocyte globulin (e. g., Thymoglobulin®), a mixture of specialized proteins called antibodies. ATG 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 T1DM. ATG can change how T cells work, and can eliminate a large proportion of the T cells from the bloodstream temporarily. Treatment of new onset T1DM with ATG 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: the Experimental Group will receive the study treatment while the Control Group that will receive 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 (e. g., glucose) 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 (MMTT). 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.

Eligibility

Minimum age: 12 Years. Maximum age: 35 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of type 1 diabetes (according to American Diabetes Association [ADA]

criteria) within100 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 Epstein-Barr virus (EBV) infection (EBV seropositive)

- Willing to use acceptable forms of contraception

Exclusion Criteria:

- Any sign of active infection (e. g., hepatitis, tuberculosis, EBV, cytomegalovirus

(CMV), or toxoplasmosis) at screening

- Positive for human immunodeficiency virus (HIV), tuberculosis, or hepatitis B surface

antigen (HBsAg) 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/┬ÁL), neutropenia (<1,500neutrophils/┬ÁL), lymphopenia

(<800 lymphocytes/┬ÁL), or thrombocytopenia (<125,000 platelets/┬ÁL).

- 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

Locations and Contacts

Children's Hospital/USC School of Medicine, Los Angeles, California 90027, United States

Children's Hospital and Research Center, Oakland, California 92609, United States

UCSD/San Diego Children's Hospital, San Diego, California 92123, United States

Diabetes Center at UCSF, San Francisco, California 94143, United States

Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado 80010, United States

Emory Children's Center, Atlanta, Georgia 30322, United States

University of Minnesota, Minneapolis, Minnesota 55455, United States

Children's Mercy Hospital, Kansas City, Missouri 64108, United States

University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Additional Information

Click here for the Immune Tolerance Network Web site

Immune Tolerance Network (ITN) TrialShare: open public access to study level information

Related publications:

Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004 Jan;53(1):250-64. Erratum in: Diabetes. 2004 Jul;53(7):1934.

Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Haastert B, Ludvigsson J, Pozzilli P, Lachin JM, Kolb H; Type 1 Diabetes Trial Net Research Group; European C-Peptide Trial Study Group. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care. 2008 Oct;31(10):1966-71. doi: 10.2337/dc07-2451. Epub 2008 Jul 15.

Starting date: August 2007
Last updated: April 10, 2015

Page last updated: August 23, 2015

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