This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at least 28 subjects will receive active Anti-Thymocyte Globulin and Granulocyte colony-stimulating factor (ATG-GCSF), at least 28 subjects will receive ATG alone and at least 28 subjects will receive placebo alone within 100 days from diagnosis of Type 1 Diabetes (T1D). The primary objective of the study will be to determine the safety and ability of low dose ATG plus GCSF and low dose ATG alone to retain/enhance C-peptide production in new onset T1D patients demonstrating residual beta cell function.
Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes
The primary statistical hypothesis to be assessed in the study is whether the 2 hour area under the curve (change in baseline to 12 months) in residual beta cell function (C-peptide) will differ between those treated with ATG and GCSF or ATG alone as compared with placebo.
The study will also examine the effect of the proposed treatments on surrogate markers for immunologic and metabolic outcomes.
Diabetes Mellitus, Type 1Type 1 Diabetes TrialNetLenograstimAntilymphocyte Serum
You can join if…
Open to people ages 12 years to 45 years
Must be> 12 years < 46
Must have a diagnosis of T1D for less than 100 days at randomization
Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age
Positive for at least one islet cell autoantibody; glutamic acid decarboxylase 65(GAD65A), Insulin micro IAA (mIAA), if obtained within 10 days of the onset of insulin therapy, islet antigen 2 (IA-2A), Islet Cell Antigen (ICA), or zinc transporter 8 (ZnT8A)
Must have stimulated C-peptide levels = 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization
Must be Epstein-Barr virus (EBV PCR) negative within two weeks of randomization if EBV seronegative at screening
Be at least 6 weeks from last live immunization
Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
Be willing to forgo vaccines during the treatment period and for 3 months following last dose of study drug
Be willing to comply with intensive diabetes management
You CAN'T join if...
Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (<3,000 leukocytes /µL), neutropenia (<1,500 neutrophils/µL), lymphopenia (<800 lymphocytes/µL), or thrombocytopenia (<100,000 platelets/µL).
Have active signs or symptoms of acute infection at the time of randomization
Have evidence of prior or current tuberculosis infection as assessed by purified protein derivative (PPD), interferon gamma release assay (IGRA) or by history
Be currently pregnant or lactating, or anticipate getting pregnant within the two year study period
Require use of other immunosuppressive agents including chronic use of systemic steroids
Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection
Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, chronic obstructive pulmonary disease (COPD), sickle cell disease,neurological, or blood count abnormalities
Have a history of malignancies other than skin
Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal
Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal
Vaccination with a live virus within the last 6 weeks
Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening
Active participation in another T1D treatment study in the previous 30 days
Prior treatment with abatacept or anti-cd3
Known allergy to GCSF or ATG
Prior treatment with ATG or known allergy to rabbit derived products
Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
University of California - San Francisco San Francisco, California, 94158, USA
Stanford University Stanford, California, 94305, USA
in progress, not accepting new patients
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)