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Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and Vitamin D3 to Children With Multiple Islet Autoantibodies (DiAPREV-IT2)

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ClinicalTrials.gov Identifier: NCT02387164
Recruitment Status : Enrolling by invitation
First Posted : March 12, 2015
Last Update Posted : August 24, 2017
Sponsor:
Collaborator:
Region Skane
Information provided by (Responsible Party):
Lund University

Brief Summary:
The purpose of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), in combination with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes in non-diabetic children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Prediabetic State Drug: Alum-GAD Drug: Vitamin D3 Phase 2

Detailed Description:

The primary objective of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), combined with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes (diagnosed according to American Diabetes Association criteria) in non-diabetic 4-17.99 year old children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.

The secondary objective is to demonstrate that treatment with Diamyd is safe in children at risk for type 1 diabetes.

The children will be followed for 5 years in the study. Primary endpoint is proportion of subjects diagnosed with type 1 diabetes in each treatment arm. Secondary endpoints are 1) safety, 2) change in metabolic status from normal to impaired glucose metabolism in the group of children with normal glucose metabolism at baseline screening.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Double-blind, Investigator-initiated Study to Determine the Effect of Alum-GAD (Diamyd) in Combination With Vitamin D3 on the Progression to Type 1 Diabetes in Children With Multiple Islet Autoantibodies
Actual Study Start Date : March 2015
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Alum-GAD, Vitamin D3
Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years.
Drug: Alum-GAD
Two doses à 20 microgram 30 days apart subcutaneously administrated
Other Names:
  • Diamyd
  • GAD-Alum
  • Alumformulated GAD

Drug: Vitamin D3
2000 Units (IE) (50 microgram) vitamin D3 daily
Other Name: Cholecalciferol

Placebo Comparator: Placebo, Vitamin D3
Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years
Drug: Vitamin D3
2000 Units (IE) (50 microgram) vitamin D3 daily
Other Name: Cholecalciferol




Primary Outcome Measures :
  1. Type 1 diabetes [ Time Frame: 5 years ]
    Proportion of subjects diagnosed with type 1 diabetes according to ADA criteria in each study arm


Secondary Outcome Measures :
  1. Impaired glucose metabolism [ Time Frame: During 5 year follow-up ]

    Change in metabolic status from normal to impaired glucose metabolism during follow-up in the group of children with normal glucose metabolism at baseline screening.

    Impaired glucose metabolism is defined as a) fasting plasma glucose 6.1 mmol/L or more, b) maximum plasma glucose 30, 60, 90 min during oral glucose tolerance test (OGTT) 11.1 mmol/L or more, c) 120 min plasma glucose on OGTT 7.8 mmol/L or more, d) HbA1c 39 mmol/L or more.


  2. Safety as measured by occurrence of adverse events [ Time Frame: 5 years follow-up ]
    Evaluation of safety of Diamyd and high dose Vitamin D3 in non-diabetic children as measured by occurrence of adverse events, injection site reactions, abnormal laboratory parameters or physical exam.



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Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children 4-17.99 years of age with positive autoantibodies to glutamate decarboxylase (GADA) and at least one additional type 1 diabetes associated autoantibody (to insulinoma associated protein 2 (IA-2A), Zinktransporter 8 (ZnT8R/Q/WA) or insulin (IAA)).
  • Written informed consent from the child and the childs legal representative(s).

Exclusion Criteria:

  1. Ongoing treatment with immunosuppressant therapy.
  2. Diabetes.
  3. Treatment with any oral or injected anti-diabetic medications
  4. Significantly abnormal hematology results at screening.
  5. Clinically significant history of acute reaction to vaccines or other drugs
  6. Treatment with any vaccine within one month prior to the first dose of the study drug or planned treatment with vaccine up to three months after the last injection with the study drug.
  7. A history of epilepsy, serious head trauma or cerebrovascular accident, or Clinical features of continuous motor unit activity in proximal muscles
  8. Participation in other Clinical trials with a new chemical entity within the previous 3 months.
  9. History of hypercalcemia.
  10. Unwilling to abstain from other medication with Vitamin D during the study period.
  11. Significant illness within 2 weeks prior to first dosing.
  12. Known Human Immuno Deficiency Virus infection or hepatitis.
  13. Presence of associated serious disease or condition.
  14. Diabetes-protective Human Leucocyte Antigen (HLA) DQ6.
  15. Females who are lactating or pregnant.
  16. Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last Diamyd administration.

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): NCT02387164


Locations
Sweden
Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11
Malmö, Sweden, 205 02
Sponsors and Collaborators
Lund University
Region Skane
Investigators
Principal Investigator: Helena Elding Larsson, MD, PhD Lund University

Additional Information:
Publications:
Ludvigsson J, Krisky D, Casas R, Battelino T, Castaño L, Greening J, Kordonouri O, Otonkoski T, Pozzilli P, Robert JJ, Veeze HJ, Palmer J, Samuelsson U, Elding Larsson H, Åman J, Kärdell G, Neiderud Helsingborg J, Lundström G, Albinsson E, Carlsson A, Nordvall M, Fors H, Arvidsson CG, Edvardson S, Hanås R, Larsson K, Rathsman B, Forsgren H, Desaix H, Forsander G, Nilsson NÖ, Åkesson CG, Keskinen P, Veijola R, Talvitie T, Raile K, Kapellen T, Burger W, Neu A, Engelsberger I, Heidtmann B, Bechtold S, Leslie D, Chiarelli F, Cicognani A, Chiumello G, Cerutti F, Zuccotti GV, Gomez Gila A, Rica I, Barrio R, Clemente M, López Garcia MJ, Rodriguez M, Gonzalez I, Lopez JP, Oyarzabal M, Reeser HM, Nuboer R, Stouthart P, Bratina N, Bratanic N, de Kerdanet M, Weill J, Ser N, Barat P, Bertrand AM, Carel JC, Reynaud R, Coutant R, Baron S. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med. 2012 Feb 2;366(5):433-42. doi: 10.1056/NEJMoa1107096.

Responsible Party: Lund University
ClinicalTrials.gov Identifier: NCT02387164     History of Changes
Other Study ID Numbers: DiAPREV/2014
First Posted: March 12, 2015    Key Record Dates
Last Update Posted: August 24, 2017
Last Verified: August 2017

Keywords provided by Lund University:
Type 1 diabetes
Islet autoantibodies
glutamate decarboxylase autoantibodies (GADA)
Immune tolerance
Prediabetes
Glucose tolerance
glutamate decarboxylase
Prevention
Children

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Aluminum sulfate
Autoantibodies
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Adjuvants, Immunologic
Immunologic Factors