T-cell targeted therapy tested in type 1 diabetes study

August 27, 2013

Results from the START clinical study (Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes), led by Dr. Steve Gitelman (University of California, San Francisco) and sponsored by the Immune Tolerance Network (ITN), are published today in The Lancet Diabetes & Endocrinology. The study did not meet its primary endpoint: at 12 months, insulin production, as measured by C-peptide responses, showed no difference in overall decline between the treatment and placebo groups.

Thymoglobulin®, currently licensed for the treatment of organ transplant rejection, is a form of antithymocyte globulin (ATG), a mixture of specialized proteins called antibodies. These antibodies attach themselves to white blood cells known as T cells, interfering with their function and eliminating them temporarily from the bloodstream. During the development of , T cells mistakenly destroy the beta cells of the pancreas, which secrete insulin. ITN investigators hypothesized that treating new-onset type 1 diabetes with thymoglobulin would disrupt T-cell activation and might induce tolerance.

The Phase II START study enrolled 58 new-onset type 1 diabetic patients ages 12 to 35 years old. The patients were randomized 2:1 to receive ATG treatment or placebo. Patients in the ATG group received intravenous infusion of ATG over 4 consecutive days at the start of the study; patients in the placebo group received saline solution. At 6-month intervals, researchers measured of patients in both groups. The study was the first rigorous, placebo-controlled, multicenter study of ATG therapy in patients with new-onset type 1 diabetes.

Further inspection of the ATG treatment group revealed two distinct rates of change during the 12-month period. Most of the decline in beta cell function occurred during the first 6 months. Interestingly, this initial rate of decline in function was limited to younger patients (ages 12 to 21 years old), whereas older patients (above 21 years of age) showed almost no reduction from baseline levels in insulin production over the 12 months. Almost all patients in the treatment group experienced serum sickness and cytokine release syndrome following ATG infusions, and the investigators suggest that this early cytokine induction may have led to the unfavorable loss of beta cell function, particularly in the younger patients.

Analyses of blood samples from START revealed that T cells rapidly decreased following ATG administration, consistent with the known mechanism of action of the drug. However, investigators observed notable differences between two specific T-cell subtypes during the first 6 months: the level of effector memory T cells, important mediators of inflammation, did not decline, while the level of regulatory T cells, which are beneficial in suppressing immune attack, were reduced.

Follow-up of subjects in this trial may yield additional insights into differences in response to ATG, and suggest biomarkers of safety and efficacy to be used in future new-onset type 1 trials. The high-quality clinical specimens collected throughout the study also will be an important resource for uncovering insights about the mechanisms of disease and identifying pathways to target in future studies.

Explore further: ITN type 1 diabetes study identifies subset of patients with strong response to therapy

Related Stories

ITN type 1 diabetes study identifies subset of patients with strong response to therapy

August 15, 2013
Primary results from a new clinical trial show that patients with type 1 diabetes treated with the monoclonal antibody teplizumab (MacroGenics, Inc.) exhibit greater preservation of C-peptide, a biomarker of islet cell function, ...

Drug preserves beta cells in new cases of type 1 diabetes

August 6, 2013
(Medical Xpress)—A drug in clinical trials has been shown to preserve insulin-producing pancreatic beta cells in nearly half of subjects newly diagnosed with type 1 diabetes. Results of the phase 2 trials are published ...

Conditioning regimen beneficial for kidney recipients

March 28, 2012
(HealthDay) -- Following a conditioning regimen of lymphoid irradiation (TLI) and antithymocyte globulin (ATG), the majority of HLA-matched kidney and hematopoietic cell transplant recipients can be withdrawn from immunosuppressive ...

Immune intervention reduces beta-cell death in type 1 diabetes

February 26, 2013
(HealthDay)—Patients recently diagnosed with type 1 diabetes have greater death of pancreatic β-cells compared with patients with long-standing diabetes, which can be reduced by treatment with teplizumab, according to ...

Antibodies from rabbits improve survival and relapse outcomes of leukemia and myelodysplasia

July 6, 2012
Researchers at Virginia Commonwealth University (VCU) Massey Cancer Center's Bone Marrow Transplant Program have demonstrated that the use of antibodies derived from rabbits can improve the survival and relapse outcomes of ...

Study shows bariatric surgery restores pancreatic function by targeting belly fat

February 26, 2013
In a substudy of the STAMPEDE trial (Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently), Cleveland Clinic researchers have found that gastric bypass surgery reverses diabetes by uniquely restoring ...

Recommended for you

Scientists discover a new way to treat type 2 diabetes

July 21, 2017
Medication currently being used to treat obesity is also proving to have significant health benefits for patients with type 2 diabetes. A new study published today in Molecular Metabolism explains how this therapeutic benefit ...

Alzheimer's drug cuts hallmark inflammation related to metabolic syndrome by 25 percent

July 20, 2017
An existing Alzheimer's medication slashes inflammation and insulin resistance in patients with metabolic syndrome, a potential therapeutic intervention for a highly dangerous condition affecting 30 percent of adults in the ...

Diabetes or its precursor affects 100 million Americans

July 19, 2017
Almost one-third of the US population—100 million people—either has diabetes or its precursor condition, known as pre-diabetes, said a government report Tuesday.

One virus may protect against type 1 diabetes, others may increase risk

July 11, 2017
Doctors can't predict who will develop type 1 diabetes, a chronic autoimmune disease in which the immune system destroys the cells needed to control blood-sugar levels, requiring daily insulin injections and continual monitoring.

Diabetes complications are a risk factor for repeat hospitalizations, study shows

July 7, 2017
For patients with diabetes, one reason for hospitalization and unplanned hospital readmission is severe dysglycemia (uncontrolled hyperglycemia - high blood sugar, or hypoglycemia - low blood sugar), says new research published ...

Researchers identify promising target to protect bone in patients with diabetes

July 7, 2017
Utilizing metabolomics research techniques, NYU Dentistry researchers investigated the underlying biochemical activity and signaling within the bone marrow of hyperglycemic mice with hopes of reducing fracture risks of diabetics

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.