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

NCT ID: NCT02352974

Last Updated: 2020-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2019-10-31

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

GAD-Alum

Intervention Type: DRUG

Vitamin D

Intervention Type: DRUG

Interventions

GAD-Alum

Intervention Type: DRUG

Vitamin D

Intervention Type: DRUG

Other Intervention Names

Diamyd; Calciferol

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Child Diabetes Foundation

OTHER

Sponsor Role: collaborator

Ostergotland County Council, Sweden

OTHER

Sponsor Role: collaborator

Diamyd Medical AB

INDUSTRY

Sponsor Role: collaborator

Johnny Ludvigsson

OTHER_GOV

Sponsor Role: lead

Responsible Party

Johnny Ludvigsson

MD, PhD, Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Johnny Ludvigsson, Professor

Role: PRINCIPAL_INVESTIGATOR

Linkoeping University

Locations

Linköping University

Linköping, , Sweden

Countries

Sweden

References

Casas R, Dietrich F, Barcenilla H, Tavira B, Wahlberg J, Achenbach P, Ludvigsson J. Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients. Front Immunol. 2020 Oct 9;11:564921. doi: 10.3389/fimmu.2020.564921. eCollection 2020.

Reference Type: DERIVED

PMID: 33162978 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30009185 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

DIAGNODE-1

Identifier Type: -

Identifier Source: org_study_id