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Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders

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Τίτλος: Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders
Συγγραφείς: Sordi V., Monti P., Lampasona V., Melzi R., Pellegrini S., Keymeulen B., Gillard P., Linn T., Bosi E., Rose L., Pozzilli P., Giorgino F., Cossu E., Piemonti L.
Συνεισφορές: Sordi, V., Monti, P., Lampasona, V., Melzi, R., Pellegrini, S., Keymeulen, B., Gillard, P., Linn, T., Bosi, E., Rose, L., Pozzilli, P., Giorgino, F., Cossu, E., Piemonti, L.
Στοιχεία εκδότη: FRONTIERS MEDIA SA
Έτος έκδοσης: 2023
Θεματικοί όροι: CXCR1, CXCR2, IL-8, post hoc analyses, trial, type 1 diabetes mellitus
Περιγραφή: AimIn a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes. We present a post hoc analysis of trial patients in the predefined subgroup analysis developed according to baseline daily insulin requirement (DIR) tertiles. MethodA double-blind, randomized (2:1), placebo-controlled study was conducted in 45 men and 31 women (aged 18-46 years) within 100 days of the first insulin administration. Patients received LDX (400 mg twice daily) for three cycles of 14 days on/14 days off, or placebo. The primary endpoint was the area under the curve for C-peptide [AUC (0-120 min)] in response to a 2-h mixed meal tolerance test (MMTT) at week 13 & PLUSMN; 1. Seventy-five patients completed the week 13 MMTT and were divided into three groups according to the DIR tertiles: lower, & LE; 0.23U/kg/die (n = 25); middle, 0.24-0.40 U/kg/die (n = 24); upper, & GE; 0.41 U/kg/die (n = 26). ResultsWhen considering the patients in the upper tertile (HIGH-DIR), C-peptide AUC (0-120 min) at 13 weeks was higher in the LDX group (n = 16) than in the placebo (n = 10) group [difference: 0.72 nmol/L (95% CI 0.9-1.34), p = 0.027]. This difference reduced over time (0.71 nmol/L at 26 weeks, p = 0.04; 0.42 nmol/L at 52 weeks, p = 0.29), while it has never been significant at any time in patients in the lower and/or middle tertile (LOW-DIR). We characterized at baseline the HIGH-DIR and found that endo-metabolic (HOMA-B, adiponectin, and glucagon-to-C-peptide ratio) and immunologic (chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP1) and Vascular Endothelial Growth Factor (VEGF)) features distinguished this group from LOW-DIR. ConclusionWhile LDX did not prevent the progressive loss of beta-cell function in the majority of treated subjects, the post hoc analysis suggests that it could work in subjects with ...
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/37409229; info:eu-repo/semantics/altIdentifier/wos/WOS:001019169200001; volume:14; firstpage:1175640; journal:FRONTIERS IN ENDOCRINOLOGY; https://hdl.handle.net/20.500.11768/148516; https://www.frontiersin.org/articles/10.3389/fendo.2023.1175640/full
DOI: 10.3389/fendo.2023.1175640
DOI: 10.3389/fendo.2023.1175640/full
Διαθεσιμότητα: https://hdl.handle.net/20.500.11768/148516
https://doi.org/10.3389/fendo.2023.1175640
https://www.frontiersin.org/articles/10.3389/fendo.2023.1175640/full
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.FD2DC481
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  Data: Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders
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  Data: <searchLink fieldCode="AR" term="%22Sordi+V%2E%22">Sordi V.</searchLink><br /><searchLink fieldCode="AR" term="%22Monti+P%2E%22">Monti P.</searchLink><br /><searchLink fieldCode="AR" term="%22Lampasona+V%2E%22">Lampasona V.</searchLink><br /><searchLink fieldCode="AR" term="%22Melzi+R%2E%22">Melzi R.</searchLink><br /><searchLink fieldCode="AR" term="%22Pellegrini+S%2E%22">Pellegrini S.</searchLink><br /><searchLink fieldCode="AR" term="%22Keymeulen+B%2E%22">Keymeulen B.</searchLink><br /><searchLink fieldCode="AR" term="%22Gillard+P%2E%22">Gillard P.</searchLink><br /><searchLink fieldCode="AR" term="%22Linn+T%2E%22">Linn T.</searchLink><br /><searchLink fieldCode="AR" term="%22Bosi+E%2E%22">Bosi E.</searchLink><br /><searchLink fieldCode="AR" term="%22Rose+L%2E%22">Rose L.</searchLink><br /><searchLink fieldCode="AR" term="%22Pozzilli+P%2E%22">Pozzilli P.</searchLink><br /><searchLink fieldCode="AR" term="%22Giorgino+F%2E%22">Giorgino F.</searchLink><br /><searchLink fieldCode="AR" term="%22Cossu+E%2E%22">Cossu E.</searchLink><br /><searchLink fieldCode="AR" term="%22Piemonti+L%2E%22">Piemonti L.</searchLink>
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  Data: Sordi, V.<br />Monti, P.<br />Lampasona, V.<br />Melzi, R.<br />Pellegrini, S.<br />Keymeulen, B.<br />Gillard, P.<br />Linn, T.<br />Bosi, E.<br />Rose, L.<br />Pozzilli, P.<br />Giorgino, F.<br />Cossu, E.<br />Piemonti, L.
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  Data: 2023
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  Data: <searchLink fieldCode="DE" term="%22CXCR1%22">CXCR1</searchLink><br /><searchLink fieldCode="DE" term="%22CXCR2%22">CXCR2</searchLink><br /><searchLink fieldCode="DE" term="%22IL-8%22">IL-8</searchLink><br /><searchLink fieldCode="DE" term="%22post+hoc+analyses%22">post hoc analyses</searchLink><br /><searchLink fieldCode="DE" term="%22trial%22">trial</searchLink><br /><searchLink fieldCode="DE" term="%22type+1+diabetes+mellitus%22">type 1 diabetes mellitus</searchLink>
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  Data: AimIn a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes. We present a post hoc analysis of trial patients in the predefined subgroup analysis developed according to baseline daily insulin requirement (DIR) tertiles. MethodA double-blind, randomized (2:1), placebo-controlled study was conducted in 45 men and 31 women (aged 18-46 years) within 100 days of the first insulin administration. Patients received LDX (400 mg twice daily) for three cycles of 14 days on/14 days off, or placebo. The primary endpoint was the area under the curve for C-peptide [AUC (0-120 min)] in response to a 2-h mixed meal tolerance test (MMTT) at week 13 & PLUSMN; 1. Seventy-five patients completed the week 13 MMTT and were divided into three groups according to the DIR tertiles: lower, & LE; 0.23U/kg/die (n = 25); middle, 0.24-0.40 U/kg/die (n = 24); upper, & GE; 0.41 U/kg/die (n = 26). ResultsWhen considering the patients in the upper tertile (HIGH-DIR), C-peptide AUC (0-120 min) at 13 weeks was higher in the LDX group (n = 16) than in the placebo (n = 10) group [difference: 0.72 nmol/L (95% CI 0.9-1.34), p = 0.027]. This difference reduced over time (0.71 nmol/L at 26 weeks, p = 0.04; 0.42 nmol/L at 52 weeks, p = 0.29), while it has never been significant at any time in patients in the lower and/or middle tertile (LOW-DIR). We characterized at baseline the HIGH-DIR and found that endo-metabolic (HOMA-B, adiponectin, and glucagon-to-C-peptide ratio) and immunologic (chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP1) and Vascular Endothelial Growth Factor (VEGF)) features distinguished this group from LOW-DIR. ConclusionWhile LDX did not prevent the progressive loss of beta-cell function in the majority of treated subjects, the post hoc analysis suggests that it could work in subjects with ...
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