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Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
J. Ludvigsson, Z. Sumnik, T. Pelikanova, L. Nattero Chavez, E. Lundberg, I. Rica, MA. Martínez-Brocca, M. Ruiz de Adana, J. Wahlberg, A. Katsarou, R. Hanas, C. Hernandez, M. Clemente León, A. Gómez-Gila, M. Lind, MF. Lozano, T. Sas, U....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
NLK
Free Medical Journals
od 1978
Open Access Digital Library
od 1978-01-01 do Před 6 měsíci
Open Access Digital Library
od 2000-01-01 do Před 6 měsíci
Medline Complete (EBSCOhost)
od 1978-01-01
PubMed
34021020
DOI
10.2337/dc21-0318
Knihovny.cz E-zdroje
- MeSH
- C-peptid MeSH
- diabetes mellitus 1. typu * farmakoterapie MeSH
- dvojitá slepá metoda MeSH
- glutamát dekarboxyláza * MeSH
- lidé MeSH
- potravní doplňky MeSH
- vitamin D MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS: In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS: Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION: Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
Department of Endocrinology and Nutrition Hospital Universitario Ramón y Cajal Madrid Spain
Department of Endocrinology and Nutrition Vall d'Hebron Hospital CIBERDEM Barcelona Spain
Department of Endocrinology Skåne University Hospital Malmö Sweden
Department of Endocrinology Virgen Macarena Hospital Sevilla Spain
Department of Medicine Department of Medicine Uddevalla Sweden
Department of Molecular and Clinical Medicine University of Gothenburg Gothenburg Sweden
Department of Pediatric Endocrinology Cruces University Hospital CIBERDEM Bilbao Spain
Department of Pediatric Endocrinology Miguel Servet University Hospital Zaragoza Spain
Department of Pediatrics NU Hospital Group Uddevalla Sweden
Diabetes Centre of the Institute of Clinical and Experimental Medicine Prague Czech Republic
Diamyd Medical AB Stockholm Sweden
Pediatric Endocrinology Service Virgen del Rocío University Hospital Sevilla Spain
Citace poskytuje Crossref.org
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