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

Study answer

What this study found

Primary end point not met in the full analysis set: treatment effect ratio 1.091 (95% CI 0.845–1.408); P = 0.501. In prespecified HLA DR3-DQ2 subgroup (n=29 active, n=17 placebo), GAD-alum significantly preserved C-peptide AUC0–120 min at 15 months (ratio 1.557; 95% CI 1.126–2.153; P = 0.0078). Higher proportion reached partial remission (IDAA1c ≤9; 78.6% vs 40.0%; P = 0.0310) and maintained stimulated C-peptide >0.2 nmol/L and 90-min C-peptide >0.2 nmol/L at 15 months (P = 0.0310, 0.0284, 0.0086). Vitamin D supplementation had no significant effect on the primary outcome across all patients…

Study & population

Multicenter, randomized, double-blind, placebo-controlled phase IIb trial; 109 participants aged 12–24 years with recent-onset type 1 diabetes (diabetes duration 7–193 days), elevated GAD65 autoantibodies, and fasting C-peptide >0.12 nmol/L; conducted at 18 clinics across the Czech Republic, the Netherlands, Spain, and Sweden.

Intervention

Three intralymphatic injections of 4 mg GAD-alum into inguinal lymph nodes on days 30, 60, and 90; oral vitamin D 2,000 IU daily for 120 days (starting day 1) if screening vitamin D < 100 nmol/L; two participants had vitamin D ≥ 100 nmol/L and received no vitamin D.

Key limitation

Not powered for the prespecified DR3-DQ2 subgroup; small subgroup size; baseline differences between groups in HbA1c and IDAA1c within the subgroup; multiple endpoints analyzed without explicit adjustment.

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Original abstract