Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes

• Status: Active, not recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Norwegian University of Science and Technology
• Collaborators: Diamyd Medical AB; Karolinska Institutet; Karolinska University Hospital; Linkoeping University; St. Olavs Hospital
• Treatments: Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

1. Signed informed consent by the patient.

2. Diagnosis of LADA and diabetes debut within the last 18 months before inclusion. LADA should be defined by the criteria of age ≥30 years at the onset of diabetes, anti-GAD positivity and no clinical need for permanent insulin treatment during the first 3 months after the diagnosis of diabetes.

3. Fasting C-peptid levels ≥ 0.3 nmol/l

4. High GADA titers (>190 U/ml)

5. Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria

6. Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria

7. Females must agree to avoid pregnancy, and must have a negative urine pregnancy test.

Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows:

For females of childbearing potential:

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives

2. combined (estrogen and progestogen containing)

3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation

4. intrauterine device

5. intrauterine hormone-releasing system (for example, progestin-releasing coil)

6. bilateral tubal occlusion

7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)

8. male partner using condom

9. abstinence from heterosexual intercourse

For males of childbearing potential:

1. condom (male)

2. abstinence from heterosexual intercourse

Exclusion Criteria:

1. Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted)

2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)

3. Systemic treatment with glucocorticoids

4. Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug

5. Antidiabetic medication (metformin excepted)

6. Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin < 12 g/L).

7. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles

8. Clinically significant history of acute reaction to vaccines in the past.

9. Renal disease (as defined by serum creatinine >150 µmol/l)

10. Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment.

11. Participation in other clinical trials with a new chemical entity within the previous 3 months

12. A history of alcohol or drug abuse

13. Known HIV or hepatitis

14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study

15. Other serious chronic disease as judged by investigator.

16. Females who are lactating, are pregnant or intend to become pregnant.

17. Inability or unwillingness to comply with the provisions of this protocol

18. Deemed by the investigator not being able to follow instructions and/or follow the study protocol

19. Treatment any other supplementation of with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 120 days daily intake of Divisun (non-investigational medicinal product)