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GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1) (DIAGNODE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02352974
Recruitment Status : Completed
First Posted : February 2, 2015
Results First Posted : April 27, 2020
Last Update Posted : April 27, 2020
Sponsor:
Collaborators:
Swedish Child Diabetes Foundation
Ostergotland County Council, Sweden
Diamyd Medical AB
Information provided by (Responsible Party):
Johnny Ludvigsson, Linkoeping University

Tracking Information
First Submitted Date  ICMJE December 9, 2014
First Posted Date  ICMJE February 2, 2015
Results First Submitted Date  ICMJE March 23, 2020
Results First Posted Date  ICMJE April 27, 2020
Last Update Posted Date April 27, 2020
Study Start Date  ICMJE January 2015
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Number of Subjects With Injection Site Reactions Month 1 [ Time Frame: Month 1 ]
    Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
  • Number of Subjects With Injection Site Reactions Month 2 [ Time Frame: Month 2 ]
    Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
  • Number of Subjects With Injection Site Reactions Month 3 [ Time Frame: Month 3 ]
    Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
  • Number of Subjects With Injection Site Reactions Month 32 [ Time Frame: Month 32, extension period ]
    Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2015)
Safety of giving Diamyd directly into lymph glands in combination with an oral vitamin D regimen at Month 6 (main study period) and Month 15 and 30 (extension study period) [ Time Frame: 6 months ]
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching); Number of adverse events and number of participants with adverse events; Laboratory measurements (biochemistry and haematology), including Calcium and Vitamin D in serum; Urinalysis (microalbuminuria, creatinine); Physical examinations, including neurological assessments; GAD65AB titer (GADA)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15 [ Time Frame: Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose ]
    Change from baseline to month 15 in C-peptide AUC (Area Under the Curve) (mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
  • Mean Change in C-peptide AUC(Mean 120min) Value, Month 30 [ Time Frame: Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose ]
    Change from baseline to month 30 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
  • Mean Change in C-peptide AUC(Mean 120min) Value, Month 43 [ Time Frame: Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose ]
    Change from baseline to month 43 in C-peptide AUC(mean 120min) value AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
  • Mean Change in C-peptide 90-minute Value, Month 15 [ Time Frame: Baseline to month 15 ]
    Change from baseline to month 15 in C-peptide 90-minute value
  • Mean Change in C-peptide 90-minute Value, Month 30 [ Time Frame: Baseline to month 30 ]
    Change from baseline to month 30 in C-peptide 90-minute value
  • Mean Change in C-peptide 90-minute Value, Month 43 [ Time Frame: Baseline to month 43, extension period ]
    Change from baseline to month 43 in C-peptide 90-minute value
  • Mean Change in Fasting C-peptide Value, Month 15 [ Time Frame: Baseline to month 15 ]
    Change from baseline to month 15 in fasting C-peptide value
  • Mean Change in Fasting C-peptide Value, Month 30 [ Time Frame: Baseline to month 30 ]
    Change from baseline to month 30 in fasting C-peptide value
  • Mean Change in Fasting C-peptide Value, Month 43 [ Time Frame: Baseline to month 43, extension period ]
    Change from baseline to month 43 in fasting C-peptide value
  • Mean Change in HbA1c, Month 15 [ Time Frame: Baseline to month 15 ]
    Change from baseline to month 15 in HbA1c
  • Mean Change in HbA1c, Month 30 [ Time Frame: Baseline to month 30 ]
    Change from baseline to month 30 in HbA1c
  • Mean Change in HbA1c, Month 43 [ Time Frame: Baseline to month 43, extension period ]
    Change from baseline to month 43 in HbA1c
  • External Insulin Dose, Baseline [ Time Frame: Baseline ]
    External insulin dose at baseline
  • External Insulin Dose, Month 15 [ Time Frame: Month 15 ]
    External insulin dose at month 15
  • External Insulin Dose, Month 30 [ Time Frame: Month 30 ]
    External insulin dose at month 30
  • External Insulin Dose, Month 43 [ Time Frame: Month 43, extension period ]
    External insulin dose at month 43
  • Mean IDAA1c Values, Baseline [ Time Frame: Baseline ]
    Insulin dose-adjusted HbA1c (IDAA1c)
  • Mean IDAA1c Values, Month 15 [ Time Frame: Month 15 ]
    Insulin dose-adjusted HbA1c (IDAA1c)
  • Mean IDAA1c Values, Month 30 [ Time Frame: Month 30 ]
    Insulin dose-adjusted HbA1c (IDAA1c)
  • Mean IDAA1c Values, Month 43 [ Time Frame: Month 43, extension period ]
    Insulin dose-adjusted HbA1c (IDAA1c)
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2015)
  • Change in immune system markers from baseline to Month 6 (main study period) and subsequent visits during the extension study period [ Time Frame: 6 months, 15 and 30 months ]
    Inflammatory markers, (e.g. TNF-alfa, IL-1 beta, IL-2, IL-17); Th2-deviation of cell-mediated immune response seen e.g. as increased ratio IL-5,10, 13 in comparison with IFN-gamma, TNF-alfa, IL-1 beta and IL-17; Regulatory T-cells
  • C-peptide: Fasting, 90 minute value, and Area Under the Curve (mean 0-120 min) during an MMTT, change from baseline [ Time Frame: 6 months, 15 and 30 months ]
  • Hemoglobin A1c (HbA1c), change from baseline [ Time Frame: 6 months, 15 and 30 months ]
  • Exogenous insulin dose per kg body weight and 24 hours, change from baseline [ Time Frame: 6 months, 15 and 30 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)
Official Title  ICMJE Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen
Brief Summary

The objectives of the main study is to:

  • Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen
  • Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion.

The objective of the sub-study is to:

  • Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study
  • Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.
Detailed Description

Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection.

A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: GAD-Alum
    Other Name: Diamyd
  • Drug: Vitamin D
    Other Name: Calciferol
Study Arms  ICMJE Experimental: GAD-Alum+Vitamin D

GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals

Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days

Interventions:
  • Drug: GAD-Alum
  • Drug: Vitamin D
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 5, 2017)
12
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2015)
5
Actual Study Completion Date  ICMJE October 2019
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Informed consent given by patients
  2. Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration
  3. Age 12.00-29.99 years at diagnosis of Type 1 diabetes
  4. Fasting C-peptide ≥0.12 nmol/L
  5. Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units
  6. Females must agree to avoid pregnancy and have a negative urine pregnancy test
  7. Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum.

Exclusion Criteria:

  1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
  2. Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
  3. Treatment with any oral or injected anti-diabetic medications other than insulin
  4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
  5. A history of anaemia or significantly abnormal haematology results at screening
  6. A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
  7. Clinically significant history of acute reaction to vaccines or other drugs in the past
  8. Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug.
  9. Participation in other clinical trials with a new chemical entity within the previous 3 months
  10. Inability or unwillingness to comply with the provisions of this protocol
  11. A history of alcohol or drug abuse
  12. A significant illness other than diabetes within 2 weeks prior to first dosing
  13. Known human immunodeficiency virus (HIV) or hepatitis
  14. Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment)
  15. Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment
  16. Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study
  17. Deemed by the investigator not being able to follow instructions and/or follow the study protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02352974
Other Study ID Numbers  ICMJE DIAGNODE-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johnny Ludvigsson, Linkoeping University
Study Sponsor  ICMJE Johnny Ludvigsson
Collaborators  ICMJE
  • Swedish Child Diabetes Foundation
  • Ostergotland County Council, Sweden
  • Diamyd Medical AB
Investigators  ICMJE
Principal Investigator: Johnny Ludvigsson, Professor Linkoeping University
PRS Account Linkoeping University
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP