Clinical trial NCT01785108: DIABGAD - Trial to Preserve Insulin Secretion in Type 1 Diabetes Using GAD-Alum (Diamyd) in Combination With Vitamin D and Ibuprofen
Official title: Pilot Trial to Preserve Residual Insulin Secretion in Children and Adolescents With Recent Onset Type 1 Diabetes by Using GAD-antigen (Diamyd) Therapy in Combination With Vitamin D and Ibuprofen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diamyd
Diabetes
Juvenile Diabetes
Diabetes type 1
Autoimmune Diabetes
Insulin dependent Diabetes
Type 1 diabetes
Type 1 diabetes mellitus
rhGAD65
GAD
GAD65
GAD-alum
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Vitamin D
Ibuprofen
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Swedish Child Diabetes Foundation
name: The Research Council of South East Sweden (FORSS)
name: Diamyd Medical AB
First posted: 2013-02-07
Enrollment: 60
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study is to

* evaluate the safety and influence of treatment with GAD-Alum (Diamyd) combined with Vitamin D and Ibuprofen on preservation of residual insulin secretion in recently diagnosed Type 1 Diabetes
* evaluate how the above mentioned treatments influence the immune system of the subjects and interact with any viral infections
* evaluate the safety and influence of treatment with double dose of GAD-Alum (Diamyd) plus Vitamin D on the immune system, viral infections, and on preservation of residual insulin secretion in recently diagnosed Type 1 Diabetes


Eligibility criteria: Main Inclusion Criteria:

* Male and female patients between 10 and 18 years of age
* Insulin dependent Type 1 Diabetes mellitus diagnosed within the previous 4 months at time of screening
* Fasting C-peptide level at time of screening above or equal to 0.12 nmol/L
* Elevated GAD65 antibodies (GADA) at time of screening

Main Exclusion Criteria:

* Treatment with immunosuppressants, continuous anti-inflammatory drug, Vitamin D or any anti-diabetic medications other than insulin
* A history of certain diseases or conditions (e.g. anemia, HIV, epilepsy, head trauma, neurological diseases or cerebrovascular accident, alcohol or drug abuse etc)
* Treatment with any vaccine within 4 months prior to first planned administration of GAD-Alum/placebo or planned treatment with vaccine up to 4 months after the last injections with GAD-Alum/Placebo, including influenza vaccines
* Participation in other clinical trials with a new chemical entity within the previous 3 months
* Pregnancy or planned pregnancy within 1 year after the last GAD-Alum/placebo dose
* Presence of associated serious disease or condition which in the opinion of the investigator makes the patient non-eligible for the study

Primary outcomes:
measure: Change in C-peptide (90 minute value and AUC mean 0-120 min) during a Mixed Meal Tolerance Test from baseline to month 6, 15 and 30
timeFrame: 6 months, 15 months and 30 months
Secondary outcomes:
measure: Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L
timeFrame: 6, 15 and 30 months
measure: Hemoglobin A1c (HbA1c), change between baseline and subsequent visits
timeFrame: 6, 15 and 30 months
measure: Exogenous insulin dose per kg body weight and 24 hours, change between baseline and subsequent visits
timeFrame: 6, 15 and 30 months
measure: Th2-deviation of cell-mediated immune response seen, e.g. as increased ratio of IL-5, 10, 13 in comparison with IFN-gamma, TNF-alfa, IL-1 beta, IL-17, and increase of T-regulatory cells
timeFrame: 6, 15 and 30 months
measure: Decrease in inflammatory markers, e.g. TNF-alfa, IL-1 beta, IL-2, IL-17
timeFrame: 6, 15 and 30 months
measure: Fasting C-peptide, change between baseline and month 6, 15 and 30
timeFrame: 6, 15 and 30 months
Other outcomes:
Locations:
city: Halmstad
country: Sweden
facility: Halmstad Hospital
city: Huddinge
country: Sweden
facility: Astrid Lindgren Children's Hospital - Huddinge
city: Kalmar
country: Sweden
facility: Kalmar Hospital
city: Linköping
country: Sweden
facility: Linköping University
city: Lund
country: Sweden
facility: Lund University Hospital
city: Malmö
country: Sweden
facility: Skåne University Hospital, UMAS
city: Stockholm
country: Sweden
facility: Sachsska, Södersjukhuset
city: Stockholm
country: Sweden
facility: Astrid Lindgren Children's Hospital
city: Uddevalla
country: Sweden
facility: Uddevalla Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Linkoeping University
name: Johnny Ludvigsson, MD,PhD,Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ludvigsson J, Routray I, Elluru S, Leanderson P, Larsson HE, Rathsman B, Hanas R, Carlsson A, Ek T, Samuelsson U, Torbjornsdotter T, Aman J, Ortqvist E, Badwal K, Beam C, Casas R. 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.
citation: Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. J Diabetes Res. 2018 May 24;2018:9391845. doi: 10.1155/2018/9391845. eCollection 2018.