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

NCT04262479 | Completed Phase 2 Results DMC

• 2 other identifiers: GADinLADA2019-002692-34
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

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.

Conditions

Latent Autoimmune Diabetes in Adults

Keywords

Glutamic Acid Decarboxylase; Alum Compounds; Injections; Inguinal Canal; Diamyd; rhGAD65; Vitamin D

Outcome Measures

Primary Outcomes (6)

• Injection Site Skin Reactions

  Injection site skin reactions 1 hour post injection, i.e., erythema, oedema, haematoa, tenderness, pain, itching or other finding.

  1 hour

• Occurrence of Adverse Events (AEs) During 5 Months From Baseline.

  AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized.

  From baseline (first injection of GAD-alum) to 5 months after baseline.

• Occurrence of Adverse Events (AEs) During the Study.

  AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit/first injection of GAD-alum). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized.

  From baseline (first injection of GAD-alum) to 12 months after baseline.

• Serum GAD65A Titers, Change From Baseline at 5 Months After Baseline.

  Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline.

  Baseline (first injection of GAD-alum) and 5 months after baseline.

• Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline.

  Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline.

  Baseline and 12 months after baseline.

• Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline.

  Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline.

  Baseline (first injection of GAD-alum) and 12 months after baseline.

Secondary Outcomes (6)

• Insulin Secretion, Change From Baseline to 5 Months After Baseline.

  Baseline (first injection of GAD-alum) and 5 months after baseline.

• Insulin Secretion, Change From Baseline to 12 Months After Baseline.

  Baseline (first injection of GAD-alum) and 12 months after baseline.

• Change in HbA1c

  from baseline to 12 months after the first injection

• Change in Fasting Glucose

  From baseline to 12 months after the first injection

• Change in Fasting C-peptide

  Between baseline and 12 months after the first injection

Study Arms (1)

GAD-vaccination with vitamin D suppletion

EXPERIMENTAL

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).

Drug: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel; Drug: Vitamin D

Interventions

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

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

Also known as: GAD-alum (Diamyd(R))

GAD-vaccination with vitamin D suppletion

Vitamin D DRUG

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

Also known as: Divisun 2000 IE

GAD-vaccination with vitamin D suppletion

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent by the patient.
• Fasting C-peptid levels ≥ 0.3 nmol/l
• High GADA titers (\>190 U/ml)
• Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria

You may not qualify if:

• 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:
• oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
• combined (estrogen and progestogen containing)
• oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
• intrauterine device
• intrauterine hormone-releasing system (for example, progestin-releasing coil)
• bilateral tubal occlusion
• vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
• male partner using condom
• abstinence from heterosexual intercourse
• For males of childbearing potential:
• condom (male)
• abstinence from heterosexual intercourse

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator
• Diamyd Medical AB: collaborator
• Karolinska Institutet: collaborator
• Linkoeping University: collaborator

Study Sites (2)

Department of Endocrinology, St Olavs Hospital

Trondheim, Norway

Location

Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute

Stockholm, Sweden

Location

Related Publications (1)

• 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.

  PMID: 31148332 BACKGROUND

MeSH Terms

Conditions

Latent Autoimmune Diabetes in Adults

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Ingrid K Hals
• Organization: NTNU

ingrid.hals@ntnu.no

+47 73412207

Study Officials

• Anne Hildur Henriksen, MD PhD

  St Olavs Hospital, Medisinsk Klinikk

  STUDY DIRECTOR

• Torstein Baade Rø, MD

  Norwegian University of Science and Technology, IKOM

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 10, 2020
• Study Start: March 2, 2020
• Primary Completion: May 5, 2022
• Study Completion: May 5, 2022
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); SE (1)