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

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ClinicalTrials.gov Identifier: NCT04262479
Recruitment Status : Recruiting
First Posted : February 10, 2020
Last Update Posted : November 4, 2020
Sponsor:
Collaborators:
St. Olavs Hospital
Diamyd Medical AB
Karolinska University Hospital
Linkoeping University
Information provided by (Responsible Party):
Norwegian University of Science and Technology

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.

Condition or disease Intervention/treatment Phase
Latent Autoimmune Diabetes in Adults Drug: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel Drug: Vitamin D Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arm Intervention/treatment
Experimental: 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).

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
Other Name: GAD-alum (Diamyd(R))

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
Other Name: Divisun 2000 IE




Primary Outcome Measures :
  1. injection site skin reactions [ Time Frame: 1 hour ]
    skin reactions 1 hour post injection vs. before injection

  2. Occurrence of adverse events (AEs) [ Time Frame: summarized at 5 months ]
    continuously monitored and registered

  3. Occurrence of adverse events (AEs) [ Time Frame: summarized at 12 months ]
    continuously monitored and registered

  4. GAD65A titer in serum [ Time Frame: at 5 months ]
    concentration in serum after the first injection vs baseline

  5. GAD65A titer in serum [ Time Frame: at 12 months ]
    concentration in serum after the first injection vs baseline


Secondary Outcome Measures :
  1. Insulin secretion [ Time Frame: 5 months after first injection ]
    measured by glucagon- and MMTT stimulated C-peptide

  2. insulin secretion [ Time Frame: 12 months after first injection ]
    measured by glucagon- and MMTT stimulated C-peptide

  3. Change in HbA1c [ Time Frame: from baseline to 5 and 12 months after the first injection ]
  4. Change in fasting glucose [ Time Frame: from baseline to 5 and 12 months after the first injection ]
  5. Change in Fasting C-peptide [ Time Frame: between baseline and 5 and 12 months after the first injection ]
  6. Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT) [ Time Frame: between baseline and 5 and 12 months after the first injection ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months 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 with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04262479


Contacts
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Contact: Ingrid Kathrin Hals, PhD +47 73412207 ingrid.hals@ntnu.no
Contact: Chandima Balasuriya, MD PhD 72829705 chandima.nirupa.dilruks.balasuriya@stolav.no

Locations
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Norway
Department of Endocrinology, St Olavs Hospital Recruiting
Trondheim, Norway
Contact: Chandima Balasuriya, MD PhD    +47 72829705    chandima.nirupa.dilruks.balasuriya@stolav.no   
Sweden
Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska University Hospital Recruiting
Stockholm, Sweden
Contact: Anneli Björklund, MD PhD         
Sponsors and Collaborators
Norwegian University of Science and Technology
St. Olavs Hospital
Diamyd Medical AB
Karolinska University Hospital
Linkoeping University
Investigators
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Study Director: Tom Christian Martinsen, MD PhD St Olavs Hospital, Medisinsk Klinikk
Study Director: Torstein Baade Rø, MD Norwegian University of Science and Technology, IKOM
Publications:
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Responsible Party: Norwegian University of Science and Technology
ClinicalTrials.gov Identifier: NCT04262479    
Other Study ID Numbers: GADinLADA
2019-002692-34 ( EudraCT Number )
First Posted: February 10, 2020    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Norwegian University of Science and Technology:
Glutamic Acid Decarboxylase
Alum Compounds
Injections
Inguinal Canal
Diamyd
rhGAD65
Vitamin D
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Latent Autoimmune Diabetes in Adults
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vitamin D
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents