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

Primary Purpose

Latent Autoimmune Diabetes in Adults

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel
Vitamin D
Sponsored by
Norwegian University of Science and Technology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Latent Autoimmune Diabetes in Adults focused on measuring Glutamic Acid Decarboxylase, Alum Compounds, Injections, Inguinal Canal, Diamyd, rhGAD65, Vitamin D

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Department of Endocrinology, St Olavs Hospital
  • Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GAD-vaccination with vitamin D suppletion

Arm Description

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).

Outcomes

Primary Outcome Measures

injection site skin reactions
skin reactions 1 hour post injection vs. before injection
Occurrence of adverse events (AEs)
continuously monitored and registered
Occurrence of adverse events (AEs)
continuously monitored and registered
GAD65A titer in serum
concentration in serum after the first injection vs baseline
GAD65A titer in serum
concentration in serum after the first injection vs baseline

Secondary Outcome Measures

Insulin secretion
measured by glucagon- and MMTT stimulated C-peptide
insulin secretion
measured by glucagon- and MMTT stimulated C-peptide
Change in HbA1c
Change in fasting glucose
Change in Fasting C-peptide
Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT)

Full Information

First Posted
February 5, 2020
Last Updated
May 25, 2022
Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, Diamyd Medical AB, Karolinska Institutet, Linkoeping University
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1. Study Identification

Unique Protocol Identification Number
NCT04262479
Brief Title
Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
March 2, 2020 (Actual)
Primary Completion Date
May 5, 2022 (Actual)
Study Completion Date
May 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian University of Science and Technology
Collaborators
St. Olavs Hospital, Diamyd Medical AB, Karolinska Institutet, Linkoeping University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Latent Autoimmune Diabetes in Adults
Keywords
Glutamic Acid Decarboxylase, Alum Compounds, Injections, Inguinal Canal, Diamyd, rhGAD65, Vitamin D

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GAD-vaccination with vitamin D suppletion
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel
Other Intervention Name(s)
GAD-alum (Diamyd(R))
Intervention Description
3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Other Intervention Name(s)
Divisun 2000 IE
Intervention Description
1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden
Primary Outcome Measure Information:
Title
injection site skin reactions
Description
skin reactions 1 hour post injection vs. before injection
Time Frame
1 hour
Title
Occurrence of adverse events (AEs)
Description
continuously monitored and registered
Time Frame
summarized at 5 months
Title
Occurrence of adverse events (AEs)
Description
continuously monitored and registered
Time Frame
summarized at 12 months
Title
GAD65A titer in serum
Description
concentration in serum after the first injection vs baseline
Time Frame
at 5 months
Title
GAD65A titer in serum
Description
concentration in serum after the first injection vs baseline
Time Frame
at 12 months
Secondary Outcome Measure Information:
Title
Insulin secretion
Description
measured by glucagon- and MMTT stimulated C-peptide
Time Frame
5 months after first injection
Title
insulin secretion
Description
measured by glucagon- and MMTT stimulated C-peptide
Time Frame
12 months after first injection
Title
Change in HbA1c
Time Frame
from baseline to 5 and 12 months after the first injection
Title
Change in fasting glucose
Time Frame
from baseline to 5 and 12 months after the first injection
Title
Change in Fasting C-peptide
Time Frame
between baseline and 5 and 12 months after the first injection
Title
Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT)
Time Frame
between baseline and 5 and 12 months after the first injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent by the patient. 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. 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 Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria 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 Exclusion Criteria: Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted) Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) Systemic treatment with glucocorticoids 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 Antidiabetic medication (metformin excepted) Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin < 12 g/L). A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles Clinically significant history of acute reaction to vaccines in the past. Renal disease (as defined by serum creatinine >150 µmol/l) Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment. Participation in other clinical trials with a new chemical entity within the previous 3 months A history of alcohol or drug abuse Known HIV or hepatitis 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 Other serious chronic disease as judged by investigator. Females who are lactating, are pregnant or intend to become pregnant. Inability or unwillingness to comply with the provisions of this protocol Deemed by the investigator not being able to follow instructions and/or follow the study protocol 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Hildur Henriksen, MD PhD
Organizational Affiliation
St Olavs Hospital, Medisinsk Klinikk
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Torstein Baade Rø, MD
Organizational Affiliation
Norwegian University of Science and Technology, IKOM
Official's Role
Study Director
Facility Information:
Facility Name
Department of Endocrinology, St Olavs Hospital
City
Trondheim
Country
Norway
Facility Name
Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute
City
Stockholm
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make IPD available.
Citations:
PubMed Identifier
31148332
Citation
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.
Results Reference
background

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

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