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

Latent Autoimmune Diabetes in Adults Clinical Trial

— GADinLADA  

Official title:

A Pilot Study on Safety, Feasibility and Insulin-promotion by Intra-inguinal Lymph Node Injections of Glutamic Acid Decarboxylase (GAD) in Patients With LADA Type of Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04262479
• Other study ID #: GADinLADA
• Secondary ID: 2019-002692-34
• Status: Completed
• Phase: Phase 2
• Start date: March 2, 2020
• Est. completion date: May 5, 2022

Study information

• Verified date: May 2022
• Source: Norwegian University of Science and Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: May 5, 2022
• Est. primary completion date: May 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Latent Autoimmune Diabetes in Adults

Intervention

Drug:
• recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel
3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden
• Vitamin D
1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden

Locations

Country	Name	City	State
Norway	Department of Endocrinology, St Olavs Hospital	Trondheim
Sweden	Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute	Stockholm

Sponsors (5)

Lead Sponsor	Collaborator
Norwegian University of Science and Technology	Diamyd Medical AB, Karolinska Institutet, Linkoeping University, St. Olavs Hospital

Countries where clinical trial is conducted

Norway,  Sweden, 

References & Publications (1)

Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Björklund A. Investigating optimal ß-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019 Oct;21(10):2219-2227. doi: 10.1111/dom.13797. Epub 2019 Jun 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	injection site skin reactions	skin reactions 1 hour post injection vs. before injection	1 hour
Primary	Occurrence of adverse events (AEs)	continuously monitored and registered	summarized at 5 months
Primary	Occurrence of adverse events (AEs)	continuously monitored and registered	summarized at 12 months
Primary	GAD65A titer in serum	concentration in serum after the first injection vs baseline	at 5 months
Primary	GAD65A titer in serum	concentration in serum after the first injection vs baseline	at 12 months
Secondary	Insulin secretion	measured by glucagon- and MMTT stimulated C-peptide	5 months after first injection
Secondary	insulin secretion	measured by glucagon- and MMTT stimulated C-peptide	12 months after first injection
Secondary	Change in HbA1c		from baseline to 5 and 12 months after the first injection
Secondary	Change in fasting glucose		from baseline to 5 and 12 months after the first injection
Secondary	Change in Fasting C-peptide		between baseline and 5 and 12 months after the first injection
Secondary	Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT)		between baseline and 5 and 12 months after the first injection