Table 1.

Active Type 1 Diabetes Immunotherapy Clinical Trials

Single Immunotherapies
Title	Intervention	Primary Outcome(s)	Secondary Outcome(s)	Registry Link
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus	Oral Insulin	Glycemic control Autoantibody status	Metabolic status	https://clinicaltrials.gov/ct2/show/NCT00419562
Fr1da Insulin Intervention	Oral Insulin	Activation of Immune Response Efficacy of Immune Response	FOXP3/IFNG gene expression IgG-binding to Insulin Circulating Insulin-tetramer positive T cells Progression to Diabetes	https://clinicaltrials.gov/ct2/show/NCT02620072
Trial of Intranasal Insulin in Children and Young Adults at Risk of Type 1 Diabetes (INITII)	Intranasal Insulin	Proportion of subjects diagnosed with type 1 diabetes	B cell function Insulin Action Circulating autoantibodies GAD-65 and IA2 T cell response	https://clinicaltrials.gov/show/NCT00336674
Teplizumab for Prevention of Type 1 Diabetes In Relatives “At-Risk”	Teplizumab	Proportion of subjects diagnosed with type 1 diabetes	Adverse effects of teplizumab	https://clinicaltrials.gov/ct2/show/NCT01030861
CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1	CTLA4-Ig (abatacept)	Change from normal glucose tolerance to abnormal glucose tolerance	Change in C-peptide to oral glucose tolerance test	https://clinicaltrials.gov/ct2/show/NCT01773707
Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus	Imatinib Mesylate	Change in baseline to 12 month 2 hour area under the curve in residual β cell function (C-peptide)	HbA1c levels C-peptide response Exogenous insulin use Number of severe hypoglycemic events Adverse effects	https://clinicaltrials.gov/ct2/show/NCT01781975
Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes	Tauroursodeoxycholic Acid (TUDCA)	Change in baseline to 6, 12, & 18 month 2 hour area under the curve in residual β cell function (C-peptide)	Endoplasmic reticulum stress Liver function	https://clinicaltrials.gov/ct2/show/NCT02218619
Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes	Bacillus Calmett-Guérin (BCG)	Improvement in HbA1c levels	Change in immune response C-peptide levels	https://clinicaltrials.gov/ct2/show/NCT02081326
Combination Immunotherapies
Title	Intervention	Primary Outcome	Secondary Outcome(s)	Registry Link
T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (TILT)	Tregs + IL-2	Adverse effects Survival of Tregs	C-peptide response Exogenous insulin use HbA1c levels Number of severe hypoglycemic events IL-2 effect on Treg kinetics β-cell death Circulating autoantibodies GAD-65, IA2, and ICA Circulating Insulin-tetramer positive T cells General immune response	https://clinicaltrials.gov/ct2/show/NCT02772679
ATG-GCSF in New Onset Type 1 Diabetes (ATG-GCSF)	Anti-tymocyte globulin (ATG) Granulocyte colony stimulating factor (GCSF)	Change in baseline to 12 month 2 hour area under the curve in residual β cell function (C-peptide)	Effect of treatment on surrogate markers for immunologic and metabolic outcomes	https://clinicaltrials.gov/ct2/show/NCT02215200
DIABGAD - Trial to Preserve Insulin Secretion in Type 1 Diabetes Using GAD-Alum (Diamyd) in Combination With Vitamin D and Ibuprofen	Glutamic Acid Decarboxylase in alum formulation (GAD-alum) Vitamin D Ibuprofen	Change in baseline to 6, 15, and 30 month 2 hour area under the curve and 90 minute value in residual β cell function (C-peptide)	Maximum C-peptide level HbA1c Exogenous insulin dose Th-2 cell-mediated immune response Circulating inflammatory markers Fasting C-peptide	https://clinicaltrials.gov/ct2/show/NCT01785108
The Use of Glutamic Acid Decarboxylase (GAD) and Gamma-Amino Butyric Acid (GABA) in the Treatment of Type I Diabetes (GABA)	Maltodextrin Glutamic Acid Decarboxylase in alum formulation (GAD-alum) Gamma-Aminobutyric Acid (GABA)	Change in baseline to 12 month total daily insulin dose requirement Change in baseline to 12 month 2 hour area under the curve residual β cell function (C-peptide)	Circulating autoantibodies GAD-65, IA2, and ICA	https://clinicaltrials.gov/ct2/show/NCT02002130
EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes	Glutamic Acid Decarboxylase in alum formulation (GAD-alum) Vitamin D Etanercept	Tolerability of combination therapy (injection site, incidence of infection, number of adverse effects, number of serious adverse effects, neurological assessments) Serum calcium and vitamin D Circulating autoantibody (GAD-65)	Change in immune system markers from baseline to 6 months (inflammatory markers, Th2 cell-mediated immune response, Tregs Change in baseline to 6, 9, 15, 30 month 2 hour area under the curve residual β cell function (C-peptide) Maximum C-peptide Exogenous insulin dose Fasting C-peptide	https://clinicaltrials.gov/ct2/show/NCT02464033
Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and Vitamin D3 to Children With Multiple Islet Autoantibodies (DiAPREV-IT2)	Glutamic Acid Decarboxylase in alum formulation (GAD-alum) Vitamin D3	Proportion of subjects diagnosed with type 1 diabetes	Change from baseline to 5 years in glucose metabolism Occurrence of adverse effects	https://www.clinicaltrials.gov/ct2/show/NCT02387164