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- Title
Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.
- Authors
Jacobsen, Laura M.; Cuthbertson, David; Bundy, Brian N.; Atkinson, Mark A.; Moore, Wayne; Haller, Michael J.; Russell, William E.; Gitelman, Stephen E.; Herold, Kevan C.; Redondo, Maria J.; Sims, Emily K.; Wherrett, Diane K.; Moran, Antoinette; Pugliese, Alberto; Gottlieb, Peter A.; Sosenko, Jay M.; Ismail, Heba M.
- Abstract
OBJECTIVE: Mixed-meal tolerance test–stimulated area under the curve (AUC) C-peptide at 12–24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. RESEARCH DESIGN AND METHODS: We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. RESULTS: Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P < 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R 2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P < 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. CONCLUSIONS: Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials.
- Subjects
TYPE 1 diabetes; PAIN tolerance; TREATMENT effectiveness; IMMUNOTHERAPY
- Publication
Diabetes Care, 2024, Vol 47, Issue 6, p1048
- ISSN
0149-5992
- Publication type
Article
- DOI
10.2337/dc24-0171