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

NCT02387164 | Terminated Phase 2 Results DMC

• 1 other identifier: DiAPREV/2014
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1; Prediabetic State

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Type 1 Diabetes Month 24

  Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24

  24 months

• Type 1 Diabetes Status Overall

  Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm overall. Including one patient diagnosed shortly after the month 24 visit.

  Over the entire study period up to 2 years

Secondary Outcomes (7)

• Number of Patients Developing Impaired Glucose Metabolism Until Month 18

  During 18 months follow-up

• Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18

  During 18 months follow-up

• Injection Site Reactions Day 1

  Day 1

• Injection Site Reactions Month 1

  Month 1

• Change From Baseline in GADA Month 1

  Month 1

Study Arms (2)

Alum-GAD, Vitamin D3

EXPERIMENTAL

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; Drug: Vitamin D3

Placebo, Vitamin D3

PLACEBO COMPARATOR

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

Interventions

Alum-GAD DRUG

Two doses à 20 microgram 30 days apart subcutaneously administrated

Also known as: Diamyd, GAD-Alum, Alumformulated GAD

Alum-GAD, Vitamin D3

Vitamin D3 DRUG

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

Also known as: Cholecalciferol

Alum-GAD, Vitamin D3; Placebo, Vitamin D3

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• Ongoing treatment with immunosuppressant therapy.
• Diabetes.
• Treatment with any oral or injected anti-diabetic medications
• Significantly abnormal hematology results at screening.
• Clinically significant history of acute reaction to vaccines or other drugs
• 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.
• A history of epilepsy, serious head trauma or cerebrovascular accident, or Clinical features of continuous motor unit activity in proximal muscles
• Participation in other Clinical trials with a new chemical entity within the previous 3 months.
• History of hypercalcemia.
• Unwilling to abstain from other medication with Vitamin D during the study period.
• Significant illness within 2 weeks prior to first dosing.
• Known Human Immuno Deficiency Virus infection or hepatitis.
• Presence of associated serious disease or condition.
• Diabetes-protective Human Leucocyte Antigen (HLA) DQ6.
• Females who are lactating or pregnant.

Sponsors & Collaborators

• Lund University: lead
• Region Skane: collaborator

Study Sites (1)

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

Malmo, 205 02, Sweden

Location

Related Publications (3)

• 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.

  PMID: 25381193 BACKGROUND

• 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.

  PMID: 23469940 BACKGROUND

• 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.

  PMID: 22296077 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Prediabetic State

Interventions

Cholecalciferol

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)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Limitations and Caveats

This study was interrupted early and terminated when only 26 out of 80 patients were enrolled. The patients were followed for 2 years rather than the planned 5 years.

Results Point of Contact

• Title: Helena Elding Larsson
• Organization: Skåne University Hospital

helena.larsson@med.lu.se

+4640337676

Study Officials

• Helena Elding Larsson, MD, PhD

  Lund University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Docent, MD, PhD

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 12, 2015
• Study Start: March 9, 2015
• Primary Completion: October 7, 2019
• Study Completion: October 7, 2019
• Last Updated: November 17, 2020
• Results First Posted: October 27, 2020

Record last verified: 2020-10

Locations

SE (1)