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Diabetes Mellitus, Type 1Phase 2DiAPREV-IT2NCT02387164

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

A Phase 2 study testing Alum-GAD and Vitamin D3 in people with Diabetes Mellitus, Type 1 and Prediabetic State, run by Lund University at 1 site in Sweden.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 4 to 18 years
Conditions the study is for
Diabetes Mellitus, Type 1, Prediabetic State
What is being tested?
Alum-GAD and Vitamin D3
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
26 participants
Where
1 siteSweden
Study dates
9 Mar 2015to 7 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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).

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last Diamyd administration.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

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

    Malmö, 205 02

Other trials in Sweden

About this study

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

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.

Read the 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.

Being tested
Alum-GAD, Vitamin D3
Keywords
Type 1 diabetes, Islet autoantibodies, glutamate decarboxylase autoantibodies (GADA), Immune tolerance, Prediabetes, Glucose tolerance, glutamate decarboxylase, Prevention, Children
Medical subject headings
Diabetes Mellitus, Type 1, Prediabetic State

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alum-GADDrug

    Also called Diamyd, GAD-Alum, Alumformulated GAD

    Two doses à 20 microgram 30 days apart subcutaneously administrated

  • Vitamin D3Drug

    Also called Cholecalciferol

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

Study groups in NCT02387164
Study groupRoleWhat they receive
Alum-GAD, Vitamin D3ExperimentalTwo 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.
Receives: Drug: Alum-GAD; Drug: Vitamin D3
Placebo, Vitamin D3Placebo comparatorTwo 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
Receives: Drug: Vitamin D3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 24 months

  2. 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.

    Measured: Over the entire study period up to 2 years

Secondary outcomes (7)

  1. Number of Patients Developing Impaired Glucose Metabolism Until Month 18

    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.

    Measured: During 18 months follow-up

  2. Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18

    Number of patients who have progression from already impaired glucose metabolism from one or several criteria to additional signs of reduced glucose metabolism (within children with impaired glucose metabolism at 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.

    Measured: During 18 months follow-up

  3. Injection Site Reactions Day 1

    Number of patients experiencing injection site reactions at day 1

    Measured: Day 1

  4. Injection Site Reactions Month 1

    Number of patients experiencing injection site reactions at month 1

    Measured: Month 1

  5. Change From Baseline in GADA Month 1

    Change from baseline to month 1 in GADA (Glutamic Acid Decarboxylase Antibodies) titers

    Measured: Month 1

  6. Change From Baseline in GADA Month 12

    Change from baseline to month 12 in GADA titers

    Measured: Month 12

  7. Change From Baseline in GADA Month 24

    Change from baseline to month 24 in GADA titers

    Measured: Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2015 (estimated)
  2. Study start9 Mar 2015
  3. Primary completion7 Oct 2019
  4. Study completion7 Oct 2019

Why it stopped: The study was interrupted early and terminated when only 26 out of 80 patients were enrolled due to new clinical study results indicating that the current study would not be informative.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02387164
Sponsor's protocol ID
DiAPREV/2014
Acronym
DiAPREV-IT2
Status last verified
Oct 2020
First submitted
5 Mar 2015
Last updated
17 Nov 2020
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25381193

  • 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.

    PubMed 23469940

  • 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.

    PubMed 22296077

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alum-GAD and Vitamin D3 in people with Diabetes Mellitus, Type 1 and Prediabetic State, run by Lund University at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Type 1 Diabetes Month 24 (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02387164, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2020.

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