scholarly journals Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

Diabetes Care ◽  
2021 ◽  
pp. dc210318
Author(s):  
Johnny Ludvigsson ◽  
Zdenek Sumnik ◽  
Terezie Pelikanova ◽  
Lia Nattero Chavez ◽  
Elena Lundberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Vitamin D Supplementation ◽  
Acid Decarboxylase ◽  
Double Blind ◽  
Recent Onset ◽  
Onset Type

scholarly journals Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial

The Lancet ◽  
2011 ◽  
Vol 378 (9788) ◽  
pp. 319-327 ◽  
Author(s):  
Diane K Wherrett ◽  
Brian Bundy ◽  
Dorothy J Becker ◽  
Linda A DiMeglio ◽  
Stephen E Gitelman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Acid Decarboxylase ◽  
Double Blind Trial ◽  
Double Blind ◽  
Recent Onset ◽  
Blind Trial ◽  
Onset Type

scholarly journals Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial

2020 ◽  
Vol 6 (7) ◽  
pp. FSO604 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Indusmita Routray ◽  
Sriramulu Elluru ◽  
Per Leanderson ◽  
Helena E Larsson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Type I Diabetes ◽  
Pilot Trial ◽  
Acid Decarboxylase ◽  
Type I ◽  
C Peptide ◽  
Recent Onset ◽  
Onset Type

Aim: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). Methods: 64 patients (T1D since <4 months, age 10–17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1–90 400 mg/day Ibuprofen, D1–450 vitamin D 2000 IU/day, D15, 45 sc. 20 μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 μg GAD-alum D15, 45; placebo. Results: Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001). Conclusion: Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 ( ClinicalTrials.gov ).

scholarly journals Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

2021 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Zdenek Sumnik ◽  
Terezie Pelikanova ◽  
Lia Nattero Chavez ◽  
Elena Lundberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
C Peptide ◽  
Recent Onset ◽  
Hla Dr3 ◽  
Effect Ratio

<b>Objectives:</b> To evaluate the efficacy of intra-lymphatic GAD-alum therapy together with vitamin D supplementation on preserving endogenous insulin secretion in all patients with Type 1 diabetes (T1D) or in a genetically pre-specified subgroup. <p><b>Research Design and Methods:</b> In a multicenter, randomized, placebo-controlled double-blind trial (NCT03345004), 109 patients aged 12-24 (16.4 ± 4.1) years with a diabetes duration of 7-193 (88.8 ± 51.4) days, elevated serum GAD65 autoantibodies (GADA) and a fasting serum C-peptide >0.12 nmol/L, were recruited. Subjects were randomized to receive either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D (2000 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-month.</p> <p><b>Results:</b> </p> <p>Primary endpoint 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 to placebo individuals with the same genotype (n=17). Several secondary end points showed supporting trends and a positive effect was seen in partial remission (IDAA1c≤9, p=0.0310). Minor transient injection site reactions were reported. </p> <p><b>Conclusions:</b> Intra-lymphatic 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.</p>

scholarly journals Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

2021 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Zdenek Sumnik ◽  
Terezie Pelikanova ◽  
Lia Nattero Chavez ◽  
Elena Lundberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
C Peptide ◽  
Recent Onset ◽  
Hla Dr3 ◽  
Effect Ratio

<b>Objectives:</b> To evaluate the efficacy of intra-lymphatic GAD-alum therapy together with vitamin D supplementation on preserving endogenous insulin secretion in all patients with Type 1 diabetes (T1D) or in a genetically pre-specified subgroup. <p><b>Research Design and Methods:</b> In a multicenter, randomized, placebo-controlled double-blind trial (NCT03345004), 109 patients aged 12-24 (16.4 ± 4.1) years with a diabetes duration of 7-193 (88.8 ± 51.4) days, elevated serum GAD65 autoantibodies (GADA) and a fasting serum C-peptide >0.12 nmol/L, were recruited. Subjects were randomized to receive either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D (2000 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-month.</p> <p><b>Results:</b> </p> <p>Primary endpoint 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 to placebo individuals with the same genotype (n=17). Several secondary end points showed supporting trends and a positive effect was seen in partial remission (IDAA1c≤9, p=0.0310). Minor transient injection site reactions were reported. </p> <p><b>Conclusions:</b> Intra-lymphatic 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.</p>

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