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

NCT ID: NCT02387164

Last Updated: 2020-11-17

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-09

Study Completion Date

2019-10-07

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 1 Prediabetic State

Keywords

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Type 1 diabetes Islet autoantibodies glutamate decarboxylase autoantibodies (GADA) Immune tolerance Prediabetes Glucose tolerance glutamate decarboxylase Prevention Children

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Alum-GAD

Intervention Type DRUG

Two doses à 20 microgram 30 days apart subcutaneously administrated

Vitamin D3

Intervention Type DRUG

2000 Units (IE) (50 microgram) vitamin D3 daily

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

Group Type PLACEBO_COMPARATOR

Vitamin D3

Intervention Type DRUG

2000 Units (IE) (50 microgram) vitamin D3 daily

Interventions

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Alum-GAD

Two doses à 20 microgram 30 days apart subcutaneously administrated

Intervention Type DRUG

Vitamin D3

2000 Units (IE) (50 microgram) vitamin D3 daily

Intervention Type DRUG

Other Intervention Names

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Diamyd GAD-Alum Alumformulated GAD Cholecalciferol

Eligibility Criteria

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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.
Minimum Eligible Age

4 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Region Skane

OTHER

Sponsor Role collaborator

Lund University

OTHER

Sponsor Role lead

Responsible Party

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Helena Elding Larsson

Docent, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Helena Elding Larsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University

Locations

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Clinical Research Center, Pediatric Endocrinology, Jan Waldenströms gata 35, 60:11

Malmo, , Sweden

Site Status

Countries

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Sweden

References

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Elding Larsson H, Larsson C, Lernmark A; DiAPREV-IT study group. Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention. Acta Diabetol. 2015 Jun;52(3):473-81. doi: 10.1007/s00592-014-0680-1. Epub 2014 Nov 8.

Reference Type BACKGROUND
PMID: 25381193 (View on PubMed)

Andersson C, Carlsson A, Cilio C, Cedervall E, Ivarsson SA, Jonsdottir B, Jonsson B, Larsson K, Neiderud J, Lernmark A, Elding Larsson H; DiAPREV-IT Study Group. Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study. Pediatr Diabetes. 2013 Aug;14(5):341-9. doi: 10.1111/pedi.12023. Epub 2013 Mar 8.

Reference Type BACKGROUND
PMID: 23469940 (View on PubMed)

Ludvigsson J, Krisky D, Casas R, Battelino T, Castano L, Greening J, Kordonouri O, Otonkoski T, Pozzilli P, Robert JJ, Veeze HJ, Palmer J, Samuelsson U, Elding Larsson H, Aman J, Kardell G, Neiderud Helsingborg J, Lundstrom G, Albinsson E, Carlsson A, Nordvall M, Fors H, Arvidsson CG, Edvardson S, Hanas R, Larsson K, Rathsman B, Forsgren H, Desaix H, Forsander G, Nilsson NO, Akesson 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, Lopez 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.

Reference Type BACKGROUND
PMID: 22296077 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.ludc.med.lu.se/research-units/diabetes-and-celiac-disease/research-projects/diabetes-prevention-immune-tolerance/

Link to the description of the first DiAPREV-IT study, that have included 50 children and is still ongoing

Other Identifiers

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DiAPREV/2014

Identifier Type: -

Identifier Source: org_study_id