PrediabetesPhase 2DIAPREV-ITNCT01122446
Diabetes Prevention - Immune Tolerance
A Phase 2 study testing Diamyd in people with Prediabetes and Type 1 Diabetes, run by Lund University at 1 site in Sweden.
Trial summary
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet… Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Prediabetes, Type 1 Diabetes
- What is being tested?
- Diamyd
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSweden
- Study dates
- Apr 2009to Dec 2016
- 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 from four (4) years of age and participating in DiPiS, TEDDY or Trial Net.
- Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb or IAA).
- Written informed consent from the child and the child's parents or legal acceptable representative(s) according to local regulations.
Who cannot join
- Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted).
- 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, other than influenza, within one month prior to the first dose of the study drug or planned treatment with vaccine up to two months after the last injection with the study drug.
Show all 12Show 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.
- Significant illness other than diabetes within 2 weeks prior to first dosing.
- Known human deficiency virus (HIV) or hepatitis.
- Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigators makes the patient non-eligible for the study.
- Diabetes-protective HLA-DQ6-genotype.
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
About this study
Official title: A Double-blind, Randomized Investigator-initiated Study to Determine the Safety and the Effect of Diamyd® on the Progression to Type 1 Diabetes in Children With Multiple Islet Cell Autoantibodies
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies
Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.
Read more
Objectives:
DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.
The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.
The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
Read the detailed description
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies
Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.
Objectives:
DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.
The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.
The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
Procedure:
50 children will be randomized to 2 injections of Diamyd® or placebo. In DIAPREV-IT we will use the previously tested dose of 20 µg Diamyd® administered as a prime-and-boost at days 1 and 30, as no serious adverse reactions have been observed with this regimen. The children will be followed every 3rd month for 5 years. Before the first injection of study drug both intravenous (IvGTT) and oral (OGTT) glucose tolerance test will be performed. These will be repeated during the study with OGTT every 6 month visit and IvGTT every full year visit.
Safety variables:
Collection of adverse events, serious adverser events, hematology, chemistry, titles of autoantibodies.
Effect variables:
The cumulative incidence of diabetes onset over time since randomization within each treatment group will be estimated using the Kaplan-Meier method (proportion surviving diabetes-free as a function of time).
Secondary efficacy variables:
Change in first-phase insulin response and K-value on IvGTT from baseline Change in fasting, 120 minutes and AUC C-peptide levels on OGTT Change in fasting, 120 minutes and AUC glucose on OGTT Change in HbA1c from baseline All measures during 5 years follow-up.
Children developing diabetes in the study will be offered to participate in a postdiagnosis protocol. Children who have had two doses of active Diamyd in the main study will be given one additional dose of 20 microgram Diamyd followed by one dose of placebo after 30 days. Children who have had two doses of placebo will be given two doses of 20 microgram Diamyd with 30 days in between. Post diagnosis follow up will proceed for at least 15 months from the first post diagnosis injection with collection of adverse events and metabolic evaluation with Mixed meal tolerance tests.
- Conditions
- Prediabetes, Type 1 Diabetes
- Being tested
- Placebo comparator, Diamyd
- Keywords
- Alum-GAD, Type 1 diabetes, prevention, immune tolerance, glucose tolerance, glutamate decarboxylase autoantibodies
- Medical subject headings
- Prediabetic State, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo comparatorOther
Placebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo.
DiamydDrug
Also called Alum-GAD
20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies.
Post diagnosis: Two doses of Diamyd followed to children originally receiving Diamyd
| Study group | Role | What they receive |
|---|---|---|
| Placebo comparator | Placebo comparator | Two doses of placebo day 1 and 30 Receives: Other: Placebo comparator |
| Alum-GAD (Diamyd) | Active comparator | 20 microgram Diamyd day 1 and 30 Receives: Drug: Diamyd |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Adverse events, serious adverse events, hematology, chemistry, autoantibody titles by treatment group
Measured: During 5 years follow up from treatment
Secondary outcomes (9)
Number of Participants With Type 1 Diabetes
Onset of Type 1 diabetes, defined according to ADA criteria, by treatment
Measured: During 5 years follow up from treatment
Fasting Glucose Over Time
Fasting glucose is measured at baseline and every 6 months within the study. Glucose is analysed by Hemocue.
Measured: During 5 year follow-up from treatment
120 Minutes Glucose From OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually. Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up.
Measured: During 5 year follow-up from treatment
AUC Glucose From OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually.
Measured: During 5 year follow-up from treatment
Fasting C-peptide Over Time
Fasting C-peptide is performed at baseline and thereafter every 6 months
Measured: During 5 year follow-up from treatment
120 Min C-peptide on OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually
Measured: During 5 year follow-up from treatment
AUC C-peptide From OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually
Measured: During 5 year follow-up from treatment
HbA1c
At all visits in the study HbA1c is measured. The change in HbA1c from baseline HbA1c is analysed at Laboratory of Clinical Chemistry, Skåne University Hospital, Malmö
Measured: During 5 year follow-up
First-phase Insulin Response From IvGTT Over Time
As secondary variables of effect we will measure the change in first-phase insulin response. In all children a baseline IvGTT is performed and after that annual IvGTT´s are performed within the study. First phase insulin response is calculated from insulin 1 and 3 minutes after the given glucose solution. Insulin is measured by Laboratory of Clinical Chemistry at Skåne University Hospital, Malmö. Change in first phase insulin response will be calculated for each individual and compared between the groups.
Measured: During 5 year follow-up from treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2010 (estimated)
- Study startApr 2009
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PrediabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lund University
- Sponsor type
- University, hospital or other
- Collaborators
- Region Skane
- Responsible party
- Principal investigator, Helena Elding Larsson, Lund University
- Investigators
- Helena Elding Larsson, MD, PhD, Principal investigator, Region Skåne and Lund University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122446
- Sponsor's protocol ID
- DIAPREV/2008
- Acronym
- DIAPREV-IT
- Status last verified
- May 2019
- First submitted
- 12 May 2010
- Last updated
- 6 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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 23469940Elding 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 25381193Elding Larsson H, Lundgren M, Jonsdottir B, Cuthbertson D, Krischer J; DiAPREV-IT Study Group. Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes: A randomized clinical trial. Pediatr Diabetes. 2018 May;19(3):410-419. doi: 10.1111/pedi.12611. Epub 2017 Nov 24.
PubMed 29171140Samuelsson H, Hojjati S, Teixeira P, Lindqvist A, Jonsson I, Lundgren M, Elding Larsson H. Delayed time to stage 3 type 1 diabetes after GAD-alum treatment in HLA-DR3-DQ2-positive children: follow-up of the randomised placebo-controlled Diabetes Prevention - Immune Tolerance trial. Diabetologia. 2026 Sep 28. doi: 10.1007/s00125-026-06875-3. Online ahead of print.
PubMed 42806034
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized Investigator-initiated Study to Determine the Safety and the Effect of Diamyd® on the Progression to Type 1 Diabetes in Children With Multiple Islet Cell Autoantibodies
- ClinicalTrials.gov ID
- NCT01122446
- Acronym / sponsor ID
- DIAPREV-IT / DIAPREV/2008
- Conditions
- Prediabetes, Type 1 Diabetes
- Keywords
- Alum-GAD, Type 1 diabetes, prevention, immune tolerance, glucose tolerance, glutamate decarboxylase autoantibodies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Lund UniversityUniversity, hospital or other
- Collaborators
- Region Skane
- Study start
- Apr 2009 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 13 May 2010 (estimated)
- Results
- Posted 6 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies
Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.
Objectives:
DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.
The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.
The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
Detailed description
A double-blind, randomized investigator-initiated study to determine the safety and the effect of Diamyd® on the progression to type 1 diabetes in children with multiple islet cell autoantibodies
Eligible children are 4 years or older, have positive GAD-antibodies and at least one additional autoantibody and not yet diabetes.
Objectives:
DiAPREV-IT is the first prevention study with Diamyd®, where the drug is given before onset of type 1 diabetes.
The primary objective is to demonstrate that Diamyd® is safe in children at risk for type 1 diabetes.
The secondary objective is to evaluate if Diamyd® may delay or stop the autoimmune process leading to clinical type 1 diabetes in children with ongoing persistent beta-cell autoimmunity as indicated by multiple positive islet cell autoantibodies.
Procedure:
50 children will be randomized to 2 injections of Diamyd® or placebo. In DIAPREV-IT we will use the previously tested dose of 20 µg Diamyd® administered as a prime-and-boost at days 1 and 30, as no serious adverse reactions have been observed with this regimen. The children will be followed every 3rd month for 5 years. Before the first injection of study drug both intravenous (IvGTT) and oral (OGTT) glucose tolerance test will be performed. These will be repeated during the study with OGTT every 6 month visit and IvGTT every full year visit.
Safety variables:
Collection of adverse events, serious adverser events, hematology, chemistry, titles of autoantibodies.
Effect variables:
The cumulative incidence of diabetes onset over time since randomization within each treatment group will be estimated using the Kaplan-Meier method (proportion surviving diabetes-free as a function of time).
Secondary efficacy variables:
Change in first-phase insulin response and K-value on IvGTT from baseline Change in fasting, 120 minutes and AUC C-peptide levels on OGTT Change in fasting, 120 minutes and AUC glucose on OGTT Change in HbA1c from baseline All measures during 5 years follow-up.
Children developing diabetes in the study will be offered to participate in a postdiagnosis protocol. Children who have had two doses of active Diamyd in the main study will be given one additional dose of 20 microgram Diamyd followed by one dose of placebo after 30 days. Children who have had two doses of placebo will be given two doses of 20 microgram Diamyd with 30 days in between. Post diagnosis follow up will proceed for at least 15 months from the first post diagnosis injection with collection of adverse events and metabolic evaluation with Mixed meal tolerance tests.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo comparator | Placebo comparator | Other: Placebo comparatorTwo doses of placebo day 1 and 30 |
| Alum-GAD (Diamyd) | Active comparator | Drug: Diamyd20 microgram Diamyd day 1 and 30 |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Children from four (4) years of age and participating in DiPiS, TEDDY or Trial Net.
- Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb or IAA).
- Written informed consent from the child and the child's parents or legal acceptable representative(s) according to local regulations.
Key exclusion criteria (12 listed)
- Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo comparatorPlacebo comparator day 1 and 30 in non-diabetic children with multiple islet autoantibodies. Post diagnosis: Two doses of 20 microgram Diamyd day 1 and 30 in children originally receiving placebo. | Other | Placebo comparator |
| DiamydAlso: Alum-GAD20 microgram day 1 and 30 in non-diabetic children with multiple islet autoantibodies. Post diagnosis: Two doses of Diamyd followed to children originally receiving Diamyd | Drug | Alum-GAD (Diamyd) |
Primary outcome
Adverse Events
Time frame: During 5 years follow up from treatment
Adverse events, serious adverse events, hematology, chemistry, autoantibody titles by treatment group
9 secondary outcomes
Number of Participants With Type 1 Diabetes
Time frame: During 5 years follow up from treatment
Fasting Glucose Over Time
Time frame: During 5 year follow-up from treatment
120 Minutes Glucose From OGTT Over Time
Time frame: During 5 year follow-up from treatment
AUC Glucose From OGTT Over Time
Time frame: During 5 year follow-up from treatment
Fasting C-peptide Over Time
Time frame: During 5 year follow-up from treatment
120 Min C-peptide on OGTT Over Time
Time frame: During 5 year follow-up from treatment
AUC C-peptide From OGTT Over Time
Time frame: During 5 year follow-up from treatment
HbA1c
Time frame: During 5 year follow-up
First-phase Insulin Response From IvGTT Over Time
Time frame: During 5 year follow-up from treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23469940Andersson 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.
- Results publication: PubMed 25381193Elding 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.
- Results publication: PubMed 29171140Elding Larsson H, Lundgren M, Jonsdottir B, Cuthbertson D, Krischer J; DiAPREV-IT Study Group. Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes: A randomized clinical trial. Pediatr Diabetes. 2018 May;19(3):410-419. doi: 10.1111/pedi.12611. Epub 2017 Nov 24.
- Derived from this study: PubMed 42806034Samuelsson H, Hojjati S, Teixeira P, Lindqvist A, Jonsson I, Lundgren M, Elding Larsson H. Delayed time to stage 3 type 1 diabetes after GAD-alum treatment in HLA-DR3-DQ2-positive children: follow-up of the randomised placebo-controlled Diabetes Prevention - Immune Tolerance trial. Diabetologia. 2026 Sep 28. doi: 10.1007/s00125-026-06875-3. Online ahead of print.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helena Elding Larsson, MD, PhD principal investigator
Region Skåne and Lund University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diamyd in people with Prediabetes and Type 1 Diabetes, 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 3 inclusion and 12 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: finished, as of the sponsor's last update on 6 May 2019. 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 6 May 2019). 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?
Adverse Events (time frame: During 5 years follow up from treatment). 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 NCT01122446, which also lists 4 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 6 May 2019; AzTrials last refreshed its copy on 30 Oct 2026.