Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes

Abstract

What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health-funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial-Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium's plans for the future.

Figure 1

Stages of diabetes and corresponding TrialNet studies. Green are completed intervention trials, purple are ongoing studies, and blue are natural history studies. *Studies in conjunction with Immune Tolerance Network. **Studies in conjunction with Diabetes Research in Children Network (DirecNet) Study Group. DZB, daclizumab; IL-2, interleukin-2; MMF, mycophenolate mofetil; NIP, Nutritional Intervention Pilot; T1D, type 1 diabetes.

Figure 2

Effects of age on progression of type 1 diabetes. A and B: Impact of age on risk for disease progression in autoantibody-positive relatives participating in the TrialNet Pathway to Prevention study. A: Life table of progression to diabetes according to age in double autoantibody–positive relatives (15). B: Life table of progression to diabetes according to age in double autoantibody–positive subjects from time of abnormal glucose tolerance (15). C: Life table of progression from randomization in stage 3 clinical trial to mixed-meal tolerance test–stimulated peak C-peptide ≤0.2 nmol/L (55). Prob., probability.