Prediabetes, Type 1 Diabetes
Conditions
Keywords
Alum-GAD, Type 1 diabetes, prevention, immune tolerance, glucose tolerance, glutamate decarboxylase autoantibodies
Brief 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 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.
Interventions
OTHERPlacebo comparator
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.
DRUGDiamyd
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
Sponsors
Region Skane
Lund University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Children from four (4) years of age and participating in DiPiS, TEDDY or Trial Net. 2. Positive GAD65Ab and at least one additional type 1 diabetes-associated autoantibody (IA-2Ab, ZnT8R/W/QAb or IAA). 3. Written informed consent from the child and the child's parents or legal acceptable representative(s) according to local regulations.
Exclusion criteria
1. Ongoing treatment with immunosuppressant therapy (topical or inhaled steroids are accepted). 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, 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. 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. Significant illness other than diabetes within 2 weeks prior to first dosing. 10. Known human deficiency virus (HIV) or hepatitis. 11. 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. 12. Diabetes-protective HLA-DQ6-genotype.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | During 5 years follow up from treatment | Adverse events, serious adverse events, hematology, chemistry, autoantibody titles by treatment group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Glucose Over Time | During 5 year follow-up from treatment | Fasting glucose is measured at baseline and every 6 months within the study. Glucose is analysed by Hemocue. |
| 120 Minutes Glucose From OGTT Over Time | During 5 year follow-up from treatment | 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. |
| AUC Glucose From OGTT Over Time | During 5 year follow-up from treatment | OGTT is performed at baseline, after 6 months and thereafter annually. |
| Fasting C-peptide Over Time | During 5 year follow-up from treatment | Fasting C-peptide is performed at baseline and thereafter every 6 months |
| Number of Participants With Type 1 Diabetes | During 5 years follow up from treatment | Onset of Type 1 diabetes, defined according to ADA criteria, by treatment |
| AUC C-peptide From OGTT Over Time | During 5 year follow-up from treatment | OGTT is performed at baseline, after 6 months and thereafter annually |
| HbA1c | During 5 year follow-up | 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 |
| First-phase Insulin Response From IvGTT Over Time | During 5 year follow-up from treatment | 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. |
| 120 Min C-peptide on OGTT Over Time | During 5 year follow-up from treatment | OGTT is performed at baseline, after 6 months and thereafter annually |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Comparator Two doses of placebo day 1 and 30
Placebo comparator: 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. | 25 |
| Alum-GAD (Diamyd) 20 microgram Diamyd day 1 and 30
Diamyd: 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 | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Alum-GAD (Diamyd) | Total | Placebo Comparator |
|---|---|---|---|
| Age, Categorical <=18 years | 25 Participants | 50 Participants | 25 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Sweden | 25 Participants | 50 Participants | 25 Participants |
| Sex: Female, Male Female | 11 Participants | 23 Participants | 12 Participants |
| Sex: Female, Male Male | 14 Participants | 27 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 25 / 25 | 25 / 25 |
| serious Total, serious adverse events | 2 / 25 | 2 / 25 |
Outcome results
Primary
Adverse Events
Adverse events, serious adverse events, hematology, chemistry, autoantibody titles by treatment group
Time frame: During 5 years follow up from treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator | Adverse Events | 2 Serious adverse events |
| Alum-GAD (Diamyd) | Adverse Events | 2 Serious adverse events |
Secondary
120 Min C-peptide on OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up. 120 min C-peptide missing at some endpoints due to missed sample
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 0 months | 1.09 nmol//L | Standard Deviation 0.6 |
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 6 months | 1.04 nmol//L | Standard Deviation 0.41 |
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 18 months | 1.27 nmol//L | Standard Deviation 0.33 |
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 30 months | 1.30 nmol//L | Standard Deviation 0.56 |
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 42 months | 1.43 nmol//L | Standard Deviation 0.58 |
| Placebo Comparator | 120 Min C-peptide on OGTT Over Time | 54 months | 1.58 nmol//L | Standard Deviation 0.7 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 42 months | 1.50 nmol//L | Standard Deviation 0.49 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 0 months | 1.22 nmol//L | Standard Deviation 0.46 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 30 months | 1.30 nmol//L | Standard Deviation 0.39 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 6 months | 1.31 nmol//L | Standard Deviation 0.5 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 54 months | 1.45 nmol//L | Standard Deviation 0.5 |
| Alum-GAD (Diamyd) | 120 Min C-peptide on OGTT Over Time | 18 months | 1.25 nmol//L | Standard Deviation 0.39 |
Secondary
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.
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 0 months | 6.88 mmol//L | Standard Deviation 1.61 |
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 6 months | 7.00 mmol//L | Standard Deviation 1.86 |
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 18 months | 7.19 mmol//L | Standard Deviation 2.05 |
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 30 months | 6.54 mmol//L | Standard Deviation 1.38 |
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 42 months | 6.63 mmol//L | Standard Deviation 2.41 |
| Placebo Comparator | 120 Minutes Glucose From OGTT Over Time | 54 months | 6.67 mmol//L | Standard Deviation 2.38 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 42 months | 6.54 mmol//L | Standard Deviation 1.3 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 0 months | 6.82 mmol//L | Standard Deviation 2.12 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 30 months | 6.31 mmol//L | Standard Deviation 1.65 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 6 months | 7.30 mmol//L | Standard Deviation 1.87 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 54 months | 7.04 mmol//L | Standard Deviation 3.11 |
| Alum-GAD (Diamyd) | 120 Minutes Glucose From OGTT Over Time | 18 months | 6.41 mmol//L | Standard Deviation 1.85 |
Secondary
AUC C-peptide From OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 6 months | 121.07 nmol*min/L | Standard Deviation 34.37 |
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 30 months | 157.35 nmol*min/L | Standard Deviation 59.83 |
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 0 months | 134.82 nmol*min/L | Standard Deviation 55.36 |
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 42 months | 169.48 nmol*min/L | Standard Deviation 65.87 |
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 18 months | 149.88 nmol*min/L | Standard Deviation 47.4 |
| Placebo Comparator | AUC C-peptide From OGTT Over Time | 54 months | 183.23 nmol*min/L | Standard Deviation 64.78 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 18 months | 152.02 nmol*min/L | Standard Deviation 52.66 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 0 months | 146.98 nmol*min/L | Standard Deviation 62.12 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 6 months | 149.01 nmol*min/L | Standard Deviation 54.66 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 54 months | 184.14 nmol*min/L | Standard Deviation 65.59 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 30 months | 172.23 nmol*min/L | Standard Deviation 50.24 |
| Alum-GAD (Diamyd) | AUC C-peptide From OGTT Over Time | 42 months | 182.14 nmol*min/L | Standard Deviation 76.33 |
Secondary
AUC Glucose From OGTT Over Time
OGTT is performed at baseline, after 6 months and thereafter annually.
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up. One child did not do OGTT at baseline and therefore the placebo group only contains 24 participants in this analysis. At 42 months one additional child only did 2 point OGTT.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | AUC Glucose From OGTT Over Time | 0 months | 989.63 mmol*min/L | Standard Deviation 207.07 |
| Placebo Comparator | AUC Glucose From OGTT Over Time | 6 months | 973.48 mmol*min/L | Standard Deviation 188.48 |
| Placebo Comparator | AUC Glucose From OGTT Over Time | 18 months | 1005.0 mmol*min/L | Standard Deviation 234.99 |
| Placebo Comparator | AUC Glucose From OGTT Over Time | 30 months | 970.81 mmol*min/L | Standard Deviation 198.96 |
| Placebo Comparator | AUC Glucose From OGTT Over Time | 42 months | 965.43 mmol*min/L | Standard Deviation 323.95 |
| Placebo Comparator | AUC Glucose From OGTT Over Time | 54 months | 949.20 mmol*min/L | Standard Deviation 263.67 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 42 months | 967.41 mmol*min/L | Standard Deviation 131.75 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 0 months | 938.72 mmol*min/L | Standard Deviation 190.87 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 30 months | 946.16 mmol*min/L | Standard Deviation 175.6 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 6 months | 960.04 mmol*min/L | Standard Deviation 182.05 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 54 months | 994.88 mmol*min/L | Standard Deviation 229.35 |
| Alum-GAD (Diamyd) | AUC Glucose From OGTT Over Time | 18 months | 904.71 mmol*min/L | Standard Deviation 210.34 |
Secondary
Fasting C-peptide Over Time
Fasting C-peptide is performed at baseline and thereafter every 6 months
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up. At 42 months one value is missing due to missed sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | Fasting C-peptide Over Time | 0 months | 0.18 nmol/L | Standard Deviation 0.09 |
| Placebo Comparator | Fasting C-peptide Over Time | 6 months | 0.21 nmol/L | Standard Deviation 0.17 |
| Placebo Comparator | Fasting C-peptide Over Time | 18 months | 0.27 nmol/L | Standard Deviation 0.18 |
| Placebo Comparator | Fasting C-peptide Over Time | 30 months | 0.34 nmol/L | Standard Deviation 0.14 |
| Placebo Comparator | Fasting C-peptide Over Time | 42 months | 0.37 nmol/L | Standard Deviation 0.17 |
| Placebo Comparator | Fasting C-peptide Over Time | 54 months | 0.48 nmol/L | Standard Deviation 0.25 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 42 months | 0.40 nmol/L | Standard Deviation 0.23 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 0 months | 0.21 nmol/L | Standard Deviation 0.1 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 30 months | 0.39 nmol/L | Standard Deviation 0.2 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 6 months | 0.26 nmol/L | Standard Deviation 0.1 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 54 months | 0.45 nmol/L | Standard Deviation 0.16 |
| Alum-GAD (Diamyd) | Fasting C-peptide Over Time | 18 months | 0.30 nmol/L | Standard Deviation 0.13 |
Secondary
Fasting Glucose Over Time
Fasting glucose is measured at baseline and every 6 months within the study. Glucose is analysed by Hemocue.
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | Fasting Glucose Over Time | 6 months | 4.98 mmol/L | Standard Deviation 0.77 |
| Placebo Comparator | Fasting Glucose Over Time | 30 months | 5.10 mmol/L | Standard Deviation 0.61 |
| Placebo Comparator | Fasting Glucose Over Time | 0 months | 4.67 mmol/L | Standard Deviation 0.56 |
| Placebo Comparator | Fasting Glucose Over Time | 42 months | 5.13 mmol/L | Standard Deviation 0.66 |
| Placebo Comparator | Fasting Glucose Over Time | 54 months | 5.29 mmol/L | Standard Deviation 0.5 |
| Placebo Comparator | Fasting Glucose Over Time | 18 months | 5.23 mmol/L | Standard Deviation 1.65 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 54 months | 5.36 mmol/L | Standard Deviation 0.39 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 0 months | 4.74 mmol/L | Standard Deviation 0.49 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 6 months | 5.04 mmol/L | Standard Deviation 0.6 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 18 months | 4.87 mmol/L | Standard Deviation 0.71 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 30 months | 5.05 mmol/L | Standard Deviation 0.68 |
| Alum-GAD (Diamyd) | Fasting Glucose Over Time | 42 months | 4.88 mmol/L | Standard Deviation 0.71 |
Secondary
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.
Time frame: During 5 year follow-up from treatment
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up. Some data missing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 24 months | 77.45 nmol/L | Standard Deviation 61.36 |
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 36 months | 70.19 nmol/L | Standard Deviation 38.55 |
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 48 months | 106.92 nmol/L | Standard Deviation 66.97 |
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 60 months | 97.60 nmol/L | Standard Deviation 63.15 |
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 0 months | 47.40 nmol/L | Standard Deviation 42.42 |
| Placebo Comparator | First-phase Insulin Response From IvGTT Over Time | 12 months | 68.57 nmol/L | Standard Deviation 54.17 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 0 months | 55.52 nmol/L | Standard Deviation 35.89 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 24 months | 70.27 nmol/L | Standard Deviation 36.61 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 60 months | 89.60 nmol/L | Standard Deviation 63.6 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 36 months | 81.06 nmol/L | Standard Deviation 37.34 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 12 months | 66.00 nmol/L | Standard Deviation 39.91 |
| Alum-GAD (Diamyd) | First-phase Insulin Response From IvGTT Over Time | 48 months | 84.75 nmol/L | Standard Deviation 37.77 |
Secondary
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
Time frame: During 5 year follow-up
Population: Children meeting the primary endpoint type 1 diabetes are not included in the analysis - therefore the number of analysed children drops during follow-up. Some data missing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator | HbA1c | 12 months | 34.92 mmol/mol | Standard Deviation 4.16 |
| Placebo Comparator | HbA1c | 6 months | 34.88 mmol/mol | Standard Deviation 2.68 |
| Placebo Comparator | HbA1c | 18 months | 36.63 mmol/mol | Standard Deviation 9.46 |
| Placebo Comparator | HbA1c | 24 months | 34.14 mmol/mol | Standard Deviation 3.23 |
| Placebo Comparator | HbA1c | 30 months | 35.19 mmol/mol | Standard Deviation 4.07 |
| Placebo Comparator | HbA1c | 36 months | 33.94 mmol/mol | Standard Deviation 4.04 |
| Placebo Comparator | HbA1c | 42 months | 33.19 mmol/mol | Standard Deviation 3.08 |
| Placebo Comparator | HbA1c | 48 months | 32.40 mmol/mol | Standard Deviation 2.95 |
| Placebo Comparator | HbA1c | 54 months | 33.73 mmol/mol | Standard Deviation 3.97 |
| Placebo Comparator | HbA1c | 60 months | 34.56 mmol/mol | Standard Deviation 4.23 |
| Placebo Comparator | HbA1c | 0 months | 33.84 mmol/mol | Standard Deviation 3.52 |
| Alum-GAD (Diamyd) | HbA1c | 48 months | 32.17 mmol/mol | Standard Deviation 2.62 |
| Alum-GAD (Diamyd) | HbA1c | 0 months | 32.76 mmol/mol | Standard Deviation 3.13 |
| Alum-GAD (Diamyd) | HbA1c | 36 months | 33.58 mmol/mol | Standard Deviation 4.34 |
| Alum-GAD (Diamyd) | HbA1c | 6 months | 33.28 mmol/mol | Standard Deviation 2.92 |
| Alum-GAD (Diamyd) | HbA1c | 12 months | 33.13 mmol/mol | Standard Deviation 3 |
| Alum-GAD (Diamyd) | HbA1c | 60 months | 34 mmol/mol | Standard Deviation 3.12 |
| Alum-GAD (Diamyd) | HbA1c | 18 months | 33.64 mmol/mol | Standard Deviation 3.36 |
| Alum-GAD (Diamyd) | HbA1c | 42 months | 32.44 mmol/mol | Standard Deviation 3.03 |
| Alum-GAD (Diamyd) | HbA1c | 24 months | 34.95 mmol/mol | Standard Deviation 6.09 |
| Alum-GAD (Diamyd) | HbA1c | 54 months | 33.75 mmol/mol | Standard Deviation 2.74 |
| Alum-GAD (Diamyd) | HbA1c | 30 months | 33.25 mmol/mol | Standard Deviation 2.81 |
Secondary
Number of Participants With Type 1 Diabetes
Onset of Type 1 diabetes, defined according to ADA criteria, by treatment
Time frame: During 5 years follow up from treatment
Population: Number of participants developing diabetes during 5 year follow up in each group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Comparator | Number of Participants With Type 1 Diabetes | 10 Participants |
| Alum-GAD (Diamyd) | Number of Participants With Type 1 Diabetes | 8 Participants |