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

Johnny Ludvigsson; Indusmita Routray; Sriramulu Elluru; Per Leanderson; Helena E Larsson; Björn Rathsman; Ragnar Hanås; Annelie Carlsson; Torben Ek; Ulf Samuelsson; Torun Torbjörnsdotter; Jan Åman; Eva Örtqvist; Karun Badwal; Craig Beam; Rosaura Casas

doi:10.2144/fsoa-2020-0078

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

Future Sci OA. 2020 Jun 23;6(7):FSO604. doi: 10.2144/fsoa-2020-0078.

Authors

Johnny Ludvigsson¹, Indusmita Routray², Sriramulu Elluru², Per Leanderson³, Helena E Larsson⁴, Björn Rathsman⁵, Ragnar Hanås⁶, Annelie Carlsson⁷, Torben Ek⁸, Ulf Samuelsson^{1

2}, Torun Torbjörnsdotter⁹, Jan Åman¹⁰, Eva Örtqvist¹¹, Karun Badwal¹², Craig Beam¹³, Rosaura Casas²

Affiliations

¹ Department of Biomedical & Clinical Sciences, Crown Princess Victoria Children´s Hospital & Div of Pediatrics, Linköping University, SE-58185, Linköping, Sweden.
² Department of Biomedical & Clinical Sciences, Division of Pediatrics, Linköping University, SE 58185 Linköping, Sweden.
³ Department of Clinical & Experimental Medicine, Occupational & Environmental Medicine Center, Linköping University, Linköping S-58185, Sweden.
⁴ Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Sweden & Department of Pediatrics, Skåne University Hospital, SE-21428 Malmö, Sweden.
⁵ Sachska Pediatric Hospital, Södersjukhuset, SE-11861 Stockholm, Sweden.
⁶ Department of Pediatrics, NU Hospital Group, SE 45153 Uddevalla, Sweden & Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, SE 41346 Gothenburg, Sweden.
⁷ Pediatric Autoimmunity, Department of Clinical Sciences Lund, Lund University, Sweden, Skåne University Hospital, SE-22242 Lund, Sweden.
⁸ Department of Pediatrics, Hospital of Halland, SE 30233 Halmstad, Sweden.
⁹ Department of Women & Child Health, Astrid Lindgrens Children's Hospital at Karolinska University Hospital, Karolinska Institutet, SE 17164 Stockholm, Sweden.
¹⁰ Department of Pediatrics, University Hospital, SE 70382 Örebro, Sweden.
¹¹ Department of Women & Child Health, Astrid Lindgren Children's Hospital at Karolinska University Hospital, Karolinska Institutet, SE 17164 Stockholm, Sweden.
¹² Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA.
¹³ Department of Biomedical Sciences, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA.

Abstract

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).

Keywords: C-peptide; GAD-alum; Type I diabetes; ibuprofen; immune response; vitamin D.

Associated data

ClinicalTrials.gov/NCT01785108