Table 1

Immune intervention trials in T1D

Study nameInterventionOutcomeResultYear reportedReference
Primary prevention studies
 Finnish TRIGR pilotCasein hydrolysate formulaAutoantibodiesApparent benefit201066
 TRIGRCasein hydrolysate formulaAutoantibodiesNo difference201467
 FINDIAInsulin-free whey-based formulaAutoantibodiesApparent benefit201268
 BABYDIETGluten-free dietAutoantibodiesNo difference201169
 TRIGRCasein hydrolysate formulaDiagnosis of T1D*Ongoing67
Secondary prevention studies
 DENISNicotinamideDiagnosis of T1DNo difference199870
 ENDITNicotinamideDiagnosis of T1DNo difference200471
 DPT-1 Parenteral InsulinInjected insulinDiagnosis of T1DNo difference200221
 DPT-1 Oral InsulinOral insulinDiagnosis of T1DNo difference200520
 Belgian parenteral insulinInjected insulinDiagnosis of T1DNo difference200951
 DIPP birth cohortNasal insulinDiagnosis of T1DNo difference200852
 DIPP sibling cohortNasal insulinDiagnosis of T1DNo difference200852
 INIT IINasal insulinDiagnosis of T1D*Ongoing60
 DIAPREV-ITGADDiagnosis of T1D*Ongoing58
 TrialNet oral insulinOral insulinDiagnosis of T1D*Ongoing59
 TrialNet teplizumabAnti-CD3, teplizumabDiagnosis of T1D*Ongoing72
 TrialNet abataceptAbataceptDiagnosis of T1D*Ongoing73
Studies in recent-onset T1D
 French cyclosporineCyclosporineRemissionBenefit19861
 Canadian-European cyclosporineCyclosporineC-pep ≥0.6 nmol/L or noninsulin treatedBenefit19882
 Azathioprine + glucocorticoidsAzathioprine and prednisonePeak C-pep/glucose ratioBenefit198874
 Azathioprine, adultsAzathioprineRemissionBenefit198575
 Azathioprine, childrenAzathioprinePartial remissionNo difference198976
 Linomide French trialLinomideGlucagon-stimulated C-pepBenefit199877
 BCGBCG vaccineGlucagon-stimulated C-pepNo difference199833
 BCGBCG vaccinePrimary, remission; secondary, MMTT C-pepNo difference199934
 French oral insulinOral insulinGlucagon-stimulated C-pepNo difference200053
 Italian oral insulinOral insulinFasting C-pepNo difference200054
 U.S. oral insulinOral insulinLoss of C-pep#200455
 Herold anti-CD3TeplizumabMMTT C-pepBenefit2002, 20053,4
 Keymeulen anti-CD3OtelixizumabC-pep after clampBenefit2005, 20105,6
 ProtégéTeplizumabInsulin <0.5 unit/kg + HbA1c <6.5%No difference2011, 201335,36
 Protégé EncoreTeplizumabInsulin <0.5 unit/kg + HbA1c <6.5%*201178
 DEFEND-1OtelixizumabMMTT C-pepNo difference201437
 DEFEND-2OtelixizumabMMTT C-pepNo difference201438
 AbATE (ITN study)TeplizumabMMTT C-pepBenefit201362
 DELAYTeplizumabMMTT C-pepBenefit201379
 GAD pilotGAD-alum vaccineFasting C-pepApparent benefit in secondary outcome in subgroup200824
 GAD TrialNetGAD-alum vaccineMMTT C-pepNo difference201112
 GAD EuropeGAD-alum vaccineMMTT C-pepNo difference201213
 GAD U.S. (DiaPrevent)GAD-alum vaccineMMTT C-pepN/A201125
 DiaPep–Israeli adultsDiaPep277 peptideGlucagon-stimulated C-pepBenefit2001, 200726,27
 DiaPep–Israeli pediatricsDiaPep277 peptideMMTT C-pepNo difference200728
 DiaPep–Belgian adultsDiaPep277 peptideGlucagon-stimulated C-pepBenefit at one dose200729
 DiaPep–Europe adultsDiaPep277 peptideGlucagon-stimulated C-pepNo difference200730
 DiaPep–Europe pediatricsDiaPep277 peptideGlucagon-stimulated C-pepNo difference200730
 DiaPep–phase IIIDiaPep277 peptideGlucagon-stimulated C-pep201414,15
 MMF/DZBMycophenolate mofetil with/without daclizumabMMTT C-pepNo difference201016
 Anti-CD20 TrialNetAnti-CD20 rituximabMMTT C-pepBenefit2009, 20147,8
 Abatacept TrialNetAbataceptMMTT C-pepBenefit2011, 20149,10
 Canakinumab TrialNetAnti-IL1β canakinumabMMTT C-pepNo difference201317
 START thymoglobulin ITNThymoglobulinMMTT C-pepNo difference201318
 T1DAL–alefacept ITNAlefaceptMMTT C-pepNo difference201319
 IL-2 & rapamycin safety ITNIL-2 and rapamycinMMTT C-pepTransient worsening201245
 AIDA anakinra trialAnakinraMMTT C-pepNo difference201317
 α1-Antitrypsinα1-AntitrypsinMMTT C-pep§201480
 Altered peptide ligandB9–23 altered peptide ligandMMTT C-pepNo difference200956
 Plasmid-encoded proinsulinPlasmid-encoded proinsulinSafety MMTT C-pep 201357
 Proinsulin peptideProinsulin peptideSafety studyNo safety issues200961
 ATG–GCSF trialATG and GCSFMMTT C-pepBenefit201511
 DIATORAtorvastatinMMTT C-pepNo difference201181
 EtanerceptEtanerceptMMTT C-pepBenefit200982
 Low-dose IL-2 safety trialIL-2 (3 doses)T-reg numberIncreased201346
 REPAIR-T1DSitagliptin and lansoprazoleMMTT C-pepNo difference201448
 AHSCT + profound immunosuppressionCyclophosphamide, GCSF, ATG, AHSCTMMTT C-pepBenefit2007, 2009, 20098385
 AHSCT + profound immunosuppressionCyclophosphamide, GCSF, ATG, AHSCTMMTT C-pepBenefit201486
 ATG–GCSF trialATG and GCSFMMTT C-pep*Ongoing87
 EXTEND trialTocilizumabMMTT C-pep*Ongoing88
 Otelixizumab dose-ranging trialOtelixizumabMMTT C-pep*Ongoing89
 α1-Antitrypsin trialα1-AntitrypsinBasal C-pep*Ongoing90
 α1-Antitrypsin trialα1-AntitrypsinMMTT C-pep*Ongoing91
 Ustekinumab pilotUstekinumabSafety*Ongoing92
 Imatinib trialImatinibMMTT C-pep*Ongoing93
 Tauroursodeoxycholic acid trialTauroursodeoxycholic acidMMTT C-pep*Ongoing94
 DIABGADGAD-alum & vitamin D with/without ibuprofenMMTT C-pep*Ongoing95
 Proinsulin peptideProinsulin peptideSafety*Ongoing96
 MethyldopaMethyldopaInhibition of DQ8 Ag*Ongoing97
 Low-dose IL-2IL-2T-reg number*Ongoing98
  • AHSCT, autologous hematopoietic stem cell transplantation; C-pep, C-peptide; INT, Immune Tolerance Network; T-reg, regulatory T cell.

  • *Data not yet available.

  • #Data ambiguous—authors claim benefit but only seen in one dose in post hoc subgroup.

  • N/A—actual data not available; press release announced negative result and study discontinuation.

  • ♓Article retracted.

  • §Data ambiguous—authors claim benefit but single-arm trial and “benefit” unclear.

  • ¶Data ambiguous (as discussed in text).