Table 1.
T1DM and Immunoregulatory Clinical Trials
| Therapy Group | Therapy | Phase | ID | Comments |
|---|---|---|---|---|
| Cytokine Blockade | Anti-IL-1β (Canakinumab) | II | No C-peptide level difference.26 | |
| IL-1R antagonist (Anakinra) | II | No C-peptide level difference.25 | ||
| Soluble TNF-α receptor (Etanercept) | I/II | Significant reduction of HA1c and increase in C-peptide levels.31 | ||
| Inducing Antigenic Tolerance | Human recombinant GAD-alum | II | Decreased Teff, increased Tregs, but no C-peptide difference.45 | |
| HSP60 (DiaPep277) | II | N/A | Delayed decrease in C-peptide levels.49 | |
| HSP60 (DiaPep277) | II | N/A | 30 children, no C-peptide, insulin dose, or HA1c level difference.48 | |
| Altered peptide ligand of B9–23 epitope (NBI-6024) | I | N/A | T cell population shift from TH1 to TH2.52 | |
| Altered peptide ligand of B9–23 epitope (NBI-6024) | I | Repeated administration shows no efficacy.53 | ||
| Multiple Islet peptide (MultPepT1De) | Ib | Recruiting.54 | ||
| Lymphocyte Modulation: T cell | Anti-CD3 (Otelixizumab) | III | No C-peptide level difference.18 | |
| Anti-CD3 (Teplizumab) | II/III | Primary outcome not met, 5% of patients were not taking insulin 1 year after treatment.19 | ||
| Anti-CD3 | II | Reduced insulin dosage requirements.63 | ||
| Anti-CD3 (Teplizumab) | II | No C-peptide level difference. Reduced insulin requirements.64 | ||
| IL-2 (Aldesleukin) | I & II | Selectively activates Tregs. No efficacy endpoints.82 | ||
| IL-2/Rapamycin combination | I | Treg, NK and Teff populations increased. B cell function impaired.84 | ||
| IL-2 (Aldesleukin) | I & II | Dosage testing. No results reported.85 | ||
| Ex vivo expanded human autologous polyclonal Tregs | I | Safe. Subset were long-lived. C-peptide levels stabilized through 2 years.73 | ||
| Ex vivo expanded CD4+CD25+CD127-Tregs | II | ISRCTN06128462 | Safe. Increased C-peptide levels. Reduced insulin requirements.87 | |
| Ex vivo expanded human Tregs | II | Follow up study. No results reported.77 | ||
| Anti-CTLA4 (Abatacept) | II | Slowed β cell reduction for 24 months, but no improved function.97 | ||
| Lymphocyte Modulation: APC | Methyldopa | Ib | Reduced inflammatory T cell response to insulin.120 | |
| Methyldopa | II | Recruiting. | ||
| Anti-CD40 ligand for Lupus | I | N/A | Terminated due to risk of life-threating thrombotic events.130 | |
| Lymphocyte Modulation: B cell | Anti-CD20 (Rituximab) | II | Inhibits T cell activation and further insulitis over a 1 year period. Follow-up study showed increase of asymptomatic viremia.146,147 | |
| Immuno-regulatory | Anti-PD1 for various cancers | N/A | N/A | Various different trials report development of insulin-dependent diabetes following anti-PD1 therapy.159 |
| Islet Protection | Tyrosine Kinase Inhibitor (Imatinib) | II | Preserved β cell function, reduced insulin requirements up to 1 year (unpublished, presented at American Diabetes Association Scientific Sessions 2017). | |
| β Cell Imaging | GLP-1R targeted probe 111In-DTPA-Exendin | N/A | Found difference in pancreatic uptake between healthy and T1D patients.262 | |
| VMAT2 targeted probe [11C]-DTBZ | N/A | Did not correlate β cell function to mass.266 |
APPROACHES FOR IMMUNOMODULATION