Objective: To evaluate safety and efficacy of ASCs infusion from healthy donors and daily cholecalciferol (VitD) supplementation in patients with recent-onset T1D, after a 6-month follow-up.
Methods: This is a phase II, prospective, one center, open trial, in which patients with recent onset T1D received one infusion of ASCs (1x106 cells/kg) and VitD 2000UI/day for 6 months. They were compared to controls with standard insulin therapy. C-peptide (CP) after mixed meal, insulin dose(UI/kg), HbA1c and CD45+CD3+CD4+FoxP3+T-cells frequencies (flow cytometry) were measured at baseline (T0) and after 3 (T3) and 6 months (T6).
Results: Eleven patients were included. Mean age and disease duration were 24.2 ± 5.2 years and 3.11 ± 0.88 months, respectively. Group 1 (n=7) received ASCs+VitD and group 2 (n=4) standard insulin therapy. Age, insulin dose, HbA1c and area under the curve (AUC) of CP were similar at T0 between groups (p=0.23, 0.23, 0.98 and 0.73, respectively). After intervention, group 1 had lower insulin requirement than group 2 at T3 (0.24±0.18 vs. 0.53±0.23IU/Kg, p=0.04) and T6 (0.24±0.15 vs. 0.66±0.33 UI/kg, p=0.04). Two patients in group 1 became transiently insulin free. HbA1C was lower in group 1 at T6 (6.77±0.79 vs. 8.75±0.95%; p=0.01). CP AUC was higher in group 1 at T3 (211.20 ± 100.42 vs. 106.05±47.25 ng/ml.min;p=0.04) and T6 (220.58 ± 97.06 vs. 63.37±37.96ng/ml.min, p=0.006). At T6, 6 patients in group 1 (85.7%) were in honeymoon phase (insulin dose ≤ 0.5IU/kg and HbA1c <7.5%) vs. none in group 2 (p=0.01). At T6 there was an inverse correlation between serum VitD and HbA1C (p=0.03; r=-0.66) and a positive correlation between VitD and CP AUC (p=0.02, r=0.67). CD45+CD3+CD4+FoxP3+ T-cells increased at T1 in group 1 (p=0.04), without differences at T3 and T6.
Conclusion: Allogenic ASCs infusion + VitD without immunosuppression was safe and may be an effective approach for the treatment of patients with recent onset T1D.
J.R. Dantas: None. D.B. Araujo: None. L.S. Baptista: None. D.L. Souto: None. K. Pereira: None. M.F. Pereira: None. C.S. Claudio-da-Silva: None. M.S. Mantuano: None. D.R. Daga: None. A.C. Senegaglia: None. C.K. Rebelatto: None. C.B. Couri: None. J.E. Oliveira: None. L. Zajdenverg: None. M. Rodacki: None.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação de Amparo a Pesquisa do Rio de Janeiro