Immune Tolerance and Type 1 Diabetes

Among the different autoimmune disorders within the Immune Tolerance Network's (ITN’s) portfolio, several studies focus on early intervention of type 1 diabetes (T1D), also called autoimmune diabetes, juvenile diabetes or insulin-dependent diabetes. This chronic inflammatory disease primarily affects children and young adults and develops when the body does not produce insulin as a result of immune system attack and destruction of the cells that make insulin.

Currently T1D is treated by life-long insulin replacement, which treats the major symptom but does not cure the underlying disease.

Research Focus - Type 1 Diabetes

Therapeutic interventions using single drug approaches in the treatment of T1D have been successful in pre-clinical studies. However, none of these immune interventions have produced a durable disease remission in patients with new onset T1D despite their ability to favorably alter the balance between the effector and regulatory arms of the immune system. Although some of the trials we have conducted demonstrate that treatment can alter the progression of the disease as measured by insulin production and usage, the changes are not long-lasting. However, these studies have provided valuable mechanistic insights regarding the effects of therapy on the immune system that will help guide the design of future treatment strategies.

To build on the insights gained investigating single agent therapies, the ITN is currently developing combination approaches that target multiple arms of the immune system, which may create a suitable environment for tolerance induction. Conceiving and implementing clinical trials with combination therapies is challenging because no single immune modulator is currently approved for use in T1D. In order to address this challenge and prioritize potential combination approaches, the ITN and JDRF have established a multi-center network for the preclinical screening of combination therapies, to measure efficacy and safety and to accelerate the transition to the clinic.

Clinical Trials - Type 1 Diabetes

Active

Inducing Remission in New Onset T1DM with Alefacept (Amevive®) (T1DAL)

Protocol Chair:
Mark Rigby, MD, PhD, Indiana University/Riley Hospital for Children, Indianapolis, IN

The purpose of this trial is to test whether a drug called alefacept will slow or halt destruction of the beta cells in the pancreas. If the destruction of the beta cells is stopped, the patients might be able to produce insulin on their own longer which could stop or slow the progression of their type 1 diabetes.

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A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part I

Protocol Chair:
Gordon Weir, Joslin Diabetes Center, Boston, MA

Terry Strom, Beth Israel Deconess, Boston, MA

The RETAIN study is evaluating a protein called alpha-1 antitrypsin (AAT) in recently diagnosed type 1 diabetes patients.

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Cytokine Production in Children with Pre-Clinical and Clinical Type 1 Insulin Dependent Diabetes Mellitus (ABBA)

Protocol Chair:
Jorma Ilonen, University of Turku, Turku, Finland

This clinical trial is being performed in collaboration with the Finnish Diabetes Prediction and Prevention project and is studying individuals in various stages of prediabetes who receive intranasal insulin as part of a secondary prevention trial. The ITN is funding the support of additional laboratory studies to identify biomarkers that can predict the onset of type 1 diabetes and to learn more about the natural history of the disease.

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Completed

Proleukin® and Rapamune® in Type 1 Diabetes Mellitus (IL2-RAPA)

Protocol Chair:
Carla Greenbaum, Benaroya Research Institute, Seattle, WA

This is a phase I trial in individuals who have been diagnosed with type 1 diabetes within the previous 3-48 months. The study is testing whether two immune system modifying drugs are safe when used in combination and if they have immune altering effects that indicate they can halt the progression of type 1 diabetes.

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Study of Thymoglobulin to Arrest Type 1 Diabetes (START)

Protocol Chair:
Stephen Gitelman, University of California, San Francisco, CA

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 3 months of diagnosis. This study is for people aged 12-35 years old.

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Autoantigen Vaccination in Human Type 1 Newly Diagnosed Diabetes Mellitus

Protocol Chair:
Tihamer Orban, Joslin Diabetes Center, Boston, MA

In addition to regulating blood sugar, insulin may have the ability to protect cells in the pancreas from attack by the immune system. This study will evaluate whether an insulin-based vaccine can protect cells from autoimmune destruction.

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Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE)

Protocol Chair:
Kevan Herold, Yale University, New Haven, CT

hOKT3gamma1 (Ala-Ala) is a man-made antibody that is commonly used to prevent organ rejection. The purpose of this study is to determine whether hOKT3gamma1 (Ala-Ala) can halt the progression of type 1 diabetes in patients diagnosed within the past 60 days.

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