DIABGAD - Trial to Preserve Insulin Secretion in Type 1 Diabetes Using GAD-Alum (Diamyd) in Combination With Vitamin D and Ibuprofen

NCT01785108 | Completed Phase 2

• 1 other identifier: DIABGAD-1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

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

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

Outcome Measures

Primary Outcomes (1)

• 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

  6 months, 15 months and 30 months

Secondary Outcomes (6)

• Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L

  6, 15 and 30 months

• Hemoglobin A1c (HbA1c), change between baseline and subsequent visits

  6, 15 and 30 months

• Exogenous insulin dose per kg body weight and 24 hours, change between baseline and subsequent visits

  6, 15 and 30 months

• 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

  6, 15 and 30 months

• Decrease in inflammatory markers, e.g. TNF-alfa, IL-1 beta, IL-2, IL-17

  6, 15 and 30 months

Study Arms (4)

GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen

ACTIVE COMPARATOR

* GAD-Alum (Diamyd) 20 µg given twice with one month interval * Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450 * Ibuprofen, 400 mg/day, from Day 1 to Day 90

Biological: GAD-Alum (Diamyd) 20 µg; Drug: Vitamin D; Drug: Ibuprofen

GAD-Alum (Diamyd) 20µg and Vitamin D

ACTIVE COMPARATOR

* GAD-Alum (Diamyd) 20 µg given twice with one month interval * Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450

Biological: GAD-Alum (Diamyd) 20 µg; Drug: Vitamin D

GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D

ACTIVE COMPARATOR

* GAD-Alum (Diamyd) 20 µg X 2 given twice with one month interval * Vitamin D oral drops, 2000 IU/day, from Day 1 to Day 450

Biological: GAD-Alum (Diamyd) 20 µg X 2; Drug: Vitamin D

Placebo

PLACEBO COMPARATOR

Biological: GAD-Alum (Diamyd) 20 µg X 2; Drug: Vitamin D; Drug: Ibuprofen

Interventions

GAD-Alum (Diamyd) 20 µg BIOLOGICAL

GAD-Alum (Diamyd) 20µg and Vitamin D; GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen

GAD-Alum (Diamyd) 20 µg X 2 BIOLOGICAL

GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D; Placebo

Vitamin D DRUG

GAD-Alum (Diamyd) 20 µg x 2 and Vitamin D; GAD-Alum (Diamyd) 20µg and Vitamin D; GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen; Placebo

Ibuprofen DRUG

GAD-Alum (Diamyd) 20µg, Vitamin D and Ibuprofen; Placebo

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnny Ludvigsson: lead
• Swedish Child Diabetes Foundation: collaborator
• The Research Council of South East Sweden (FORSS): collaborator
• Diamyd Medical AB: collaborator

Study Sites (10)

Halmstad Hospital

Halmstad, SE-301 85, Sweden

Location

Astrid Lindgren Children's Hospital - Huddinge

Huddinge, SE-141 86, Sweden

Location

Kalmar Hospital

Kalmar, SE-391 85, Sweden

Location

Linköping University

Linköping, SE-581 85, Sweden

Location

Lund University Hospital

Lund, SE-221 85, Sweden

Location

Skåne University Hospital, UMAS

Malmo, SE-205 02, Sweden

Location

Örebro University Hospital

Örebro, SE-701 85, Sweden

Location

Sachsska, Södersjukhuset

Stockholm, SE-118 83, Sweden

Location

Astrid Lindgren Children's Hospital

Stockholm, SE-171 76, Sweden

Location

Uddevalla Hospital

Uddevalla, SE-451 80, Sweden

Location

Related Publications (2)

• 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.

  PMID: 32802401 DERIVED

• 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.

  PMID: 30009185 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases

Interventions

Vitamin D; Ibuprofen

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Johnny Ludvigsson, MD,PhD,Prof

  Linkoeping University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: February 1, 2013
• First Posted: February 7, 2013
• Study Start: February 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: August 23, 2017

Record last verified: 2017-08

Locations

SE (10)