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

NCT ID: NCT04262479

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-02
• Study Completion Date: 2022-05-05

Brief 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.

Detailed Description

The purpose of the trial is to evaluate the effects of 3 intra-nodal injections of GAD-alum, together with oral vitamin D supplementation, in a population of LADA patients with high GADA titers. Effects will be summarized at 5 and 12 months after the first injection.

• The primary objective is to evaluate safety and feasibility of this treatment regimen.
• Secondary objectives are to test if the treatment induces a strong GAD-specific immune response similar to what has previously been observed in type 1 diabetes patients and to test for indications of preservation of endogenous insulin production.

The study is an open label Phase IIa feasibility trial. It is a pilot study that does not include a placebo arm.

Antidiabetic medication in the form of metformin is acceptable before and during the trial. Study participants must be insulin independent at baseline, but if the need for insulin treatment develops during the trial, such treatment will be given.

GAD-alum will be injected directly into an inguinal lymph node by a qualified radiologist.

Patients will be followed for a total of 12 months during which their endogenous insulin production and immune response will be evaluated at regular intervals throughout the study period. Urine and blood samples will be taken for safety, diabetes status assessments, vitamin D levels and immunological assessments. Concomitant medication and demographics will be collected.

Conditions

Latent Autoimmune Diabetes in Adults

Study Design

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

Study Groups

GAD-vaccination with vitamin D suppletion

Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart.

Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).

Group Type: EXPERIMENTAL

recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel

Intervention Type: DRUG

3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden

Vitamin D

Intervention Type: DRUG

1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden

Interventions

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

Intervention Type: DRUG

Vitamin D

1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden

Intervention Type: DRUG

Other Intervention Names

GAD-alum (Diamyd(R)); Divisun 2000 IE

Eligibility 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

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

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)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Diamyd Medical AB

INDUSTRY

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Linkoeping University

OTHER_GOV

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Hildur Henriksen, MD PhD

Role: STUDY_DIRECTOR

St Olavs Hospital, Medisinsk Klinikk

Torstein Baade Rø, MD

Role: STUDY_DIRECTOR

Norwegian University of Science and Technology, IKOM

Locations

Department of Endocrinology, St Olavs Hospital

Trondheim, , Norway

Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute

Stockholm, , Sweden

Countries

Norway; Sweden

References

Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Bjorklund A. Investigating optimal beta-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.

Reference Type: BACKGROUND

PMID: 31148332 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019-002692-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GADinLADA

Identifier Type: -

Identifier Source: org_study_id