Diabetes Mellitus, Type 1Phase 1DIAGNODENCT02352974
GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes (DIAGNODE-1)
A Phase 1 study testing GAD-Alum and Vitamin D in people with Diabetes Mellitus, Type 1, run by Johnny Ludvigsson at 1 site in Sweden.
Trial summary
The objectives of the main study is to: Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion. Read more about this study
- Who is it for?
- Ages 12 to 30 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- GAD-Alum and Vitamin D
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSweden
- Study dates
- Jan 2015to Oct 2019
- Phase
- Phase 1
- 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 12 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Informed consent given by patients
- Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration
- Age 12.00-29.99 years at diagnosis of Type 1 diabetes
- Fasting C-peptide ≥0.12 nmol/L
- Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units
- Females must agree to avoid pregnancy and have a negative urine pregnancy test
- Patients of childbearing potential must agree to using adequate contraception, until 1 year after the last administration of GAD-Alum.
Who cannot join
- Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
- Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- Treatment with any oral or injected anti-diabetic medications other than insulin
- Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
- A history of anaemia or significantly abnormal haematology results at screening
- A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
Show all 17Show fewer
- Clinically significant history of acute reaction to vaccines or other drugs in the past
- Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug.
- Participation in other clinical trials with a new chemical entity within the previous 3 months
- Inability or unwillingness to comply with the provisions of this protocol
- A history of alcohol or drug abuse
- A significant illness other than diabetes within 2 weeks prior to first dosing
- Known human immunodeficiency virus (HIV) or hepatitis
- Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG (beta-human chorionic gonadotropin) on-site within 24 hours prior to the GAD-Alum treatment)
- Males or females not willing to use adequate contraception until 1 year after the last GAD-Alum treatment
- Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study
- Deemed by the investigator not being able to follow instructions and/or follow the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen
The objectives of the main study is to:
- Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen
- Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion.
The objective of the sub-study is to:
- Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study
- Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.
Read the detailed description
Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection.
A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- GAD-Alum, Vitamin D
- Keywords
- Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus, rhGAD65 (Recombinant Human GAD with molecular mass 65,000), GAD65, GAD-Alum, Diabetes Mellitus, Diabetes mellitus Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Vitamin D
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GAD-AlumDrug
Also called Diamyd
Vitamin DDrug
Also called Calciferol
| Study group | Role | What they receive |
|---|---|---|
| GAD-Alum+Vitamin D | Experimental | GAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals
Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days Receives: Drug: GAD-Alum; Drug: Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Injection Site Reactions Month 1
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Measured: Month 1
Number of Subjects With Injection Site Reactions Month 2
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Measured: Month 2
Number of Subjects With Injection Site Reactions Month 3
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Measured: Month 3
Number of Subjects With Injection Site Reactions Month 32
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Measured: Month 32, extension period
Secondary outcomes (20)
Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15
Change from baseline to month 15 in C-peptide AUC (Area Under the Curve) (mean 120min) value
AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Measured: Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide AUC(Mean 120min) Value, Month 30
Change from baseline to month 30 in C-peptide AUC(mean 120min) value
AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Measured: Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide AUC(Mean 120min) Value, Month 43
Change from baseline to month 43 in C-peptide AUC(mean 120min) value
AUC (mean 120min) (nmol/L) is the C-peptide AUC during an MMTT (nmol/L*minutes) divided by the duration of the MMTT (minutes) i.e. C-peptide weighted average concentration
Measured: Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide 90-minute Value, Month 15
Change from baseline to month 15 in C-peptide 90-minute value
Measured: Baseline to month 15
Mean Change in C-peptide 90-minute Value, Month 30
Change from baseline to month 30 in C-peptide 90-minute value
Measured: Baseline to month 30
Mean Change in C-peptide 90-minute Value, Month 43
Change from baseline to month 43 in C-peptide 90-minute value
Measured: Baseline to month 43, extension period
Mean Change in Fasting C-peptide Value, Month 15
Change from baseline to month 15 in fasting C-peptide value
Measured: Baseline to month 15
Mean Change in Fasting C-peptide Value, Month 30
Change from baseline to month 30 in fasting C-peptide value
Measured: Baseline to month 30
Mean Change in Fasting C-peptide Value, Month 43
Change from baseline to month 43 in fasting C-peptide value
Measured: Baseline to month 43, extension period
Mean Change in HbA1c, Month 15
Change from baseline to month 15 in HbA1c
Measured: Baseline to month 15
Mean Change in HbA1c, Month 30
Change from baseline to month 30 in HbA1c
Measured: Baseline to month 30
Mean Change in HbA1c, Month 43
Change from baseline to month 43 in HbA1c
Measured: Baseline to month 43, extension period
External Insulin Dose, Baseline
External insulin dose at baseline
Measured: Baseline
External Insulin Dose, Month 15
External insulin dose at month 15
Measured: Month 15
External Insulin Dose, Month 30
External insulin dose at month 30
Measured: Month 30
External Insulin Dose, Month 43
External insulin dose at month 43
Measured: Month 43, extension period
Mean IDAA1c Values, Baseline
Insulin dose-adjusted HbA1c (IDAA1c)
Measured: Baseline
Mean IDAA1c Values, Month 15
Insulin dose-adjusted HbA1c (IDAA1c)
Measured: Month 15
Mean IDAA1c Values, Month 30
Insulin dose-adjusted HbA1c (IDAA1c)
Measured: Month 30
Mean IDAA1c Values, Month 43
Insulin dose-adjusted HbA1c (IDAA1c)
Measured: Month 43, extension period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionOct 2019
- Study completionOct 2019
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 (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johnny Ludvigsson
- Sponsor type
- Other government
- Collaborators
- Swedish Child Diabetes Foundation, Ostergotland County Council, Sweden, Diamyd Medical AB
- Responsible party
- Sponsor-investigator, Johnny Ludvigsson, Linkoeping University
- Investigators
- Johnny Ludvigsson, Professor, Principal investigator, Linkoeping University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02352974
- Sponsor's protocol ID
- DIAGNODE-1
- Acronym
- DIAGNODE
- Status last verified
- Apr 2020
- First submitted
- 9 Dec 2014
- Last updated
- 27 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Casas R, Dietrich F, Barcenilla H, Tavira B, Wahlberg J, Achenbach P, Ludvigsson J. Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients. Front Immunol. 2020 Oct 9;11:564921. doi: 10.3389/fimmu.2020.564921. eCollection 2020.
PubMed 33162978Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. J Diabetes Res. 2018 May 24;2018:9391845. doi: 10.1155/2018/9391845. eCollection 2018.
PubMed 30009185
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd®) Therapy Administered Into Lymph Nodes in Combination With an Oral Vitamin D Regimen
- ClinicalTrials.gov ID
- NCT02352974
- Acronym / sponsor ID
- DIAGNODE / DIAGNODE-1
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diamyd, Diabetes, Juvenile Diabetes, Diabetes Type 1, Type 1 Diabetes, Autoimmune Diabetes, Insulin Dependent Diabetes, Type 1 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Johnny LudvigssonOther government
- Collaborators
- Swedish Child Diabetes Foundation, Ostergotland County Council, Sweden, Diamyd Medical AB
- Study start
- Jan 2015
- Primary completion
- Oct 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 2 Feb 2015 (estimated)
- Results
- Posted 27 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of the main study is to:
- Evaluate the safety of giving GAD-Alum (Glutamic acid decarboxylase) (Diamyd) directly into lymph glands in combination with an oral vitamin D regimen
- Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion.
The objective of the sub-study is to:
- Evaluate safety after a fourth injection with 4 μg GAD-Alum direct into an inguinal lymph gland in 3 adult patients from the main study
- Evaluate how the above mentioned treatment influences the immune system and endogenous insulin secretion.
Detailed description
Eligible patients will be treated with 4 µg GAD-Alum into an inguinal lymph gland at three occasions, with one month intervals in combination with Vitamin D (14 000 IU/week) for 4 months, starting 1 month prior to first GAD-Alum injection.
A sub-study will include three adult patients from the main study and evaluate safety after a fourth injection with 4 μg GAD-Alum into an inguinal lymph gland in combination with oral vitamin D intake. The Prolonged Extension Study Period is 12 months and will start 30,5 months after baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GAD-Alum+Vitamin D | Experimental | Drug: GAD-Alum, Drug: Vitamin DGAD-Alum (Diamyd) injected into Lymph Nodes Dosage and interval: One injection of 4 µg Diamyd will be administered into the lymph nodes at three occasions, with one month intervals Vitamin D (Calciferol) in oral solution. Dosage and interval: 2000 IU daily for 120 days |
Who may qualify
- Ages
- 12 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Informed consent given by patients
- Type 1 diabetes according to the ADA (American Diabetes Association) classification with < 6 months diabetes duration
- Age 12.00-29.99 years at diagnosis of Type 1 diabetes
- Fasting C-peptide ≥0.12 nmol/L
- Pos GADA(Antibodies to GAD with molecular mass 65,000) but < 50 000 random units
Key exclusion criteria (17 listed)
- Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
- Continuous treatment with any inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- Treatment with any oral or injected anti-diabetic medications other than insulin
- Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
- A history of anaemia or significantly abnormal haematology results at screening
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 |
|---|---|---|
| GAD-AlumAlso: Diamyd | Drug | GAD-Alum+Vitamin D |
| Vitamin DAlso: Calciferol | Drug | GAD-Alum+Vitamin D |
Primary outcome
Number of Subjects With Injection Site Reactions Month 1
Time frame: Month 1
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 2
Time frame: Month 2
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 3
Time frame: Month 3
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
Number of Subjects With Injection Site Reactions Month 32
Time frame: Month 32, extension period
Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)
20 secondary outcomes
Mean Change in C-peptide AUC (Area Under the Curve) (Mean 120min) Value, Month 15
Time frame: Baseline to month 15 at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide AUC(Mean 120min) Value, Month 30
Time frame: Baseline to month 30 at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide AUC(Mean 120min) Value, Month 43
Time frame: Baseline to month 43, extension period at 0, 30, 60, 90, 120 minutes post-dose
Mean Change in C-peptide 90-minute Value, Month 15
Time frame: Baseline to month 15
Mean Change in C-peptide 90-minute Value, Month 30
Time frame: Baseline to month 30
Mean Change in C-peptide 90-minute Value, Month 43
Time frame: Baseline to month 43, extension period
Mean Change in Fasting C-peptide Value, Month 15
Time frame: Baseline to month 15
Mean Change in Fasting C-peptide Value, Month 30
Time frame: Baseline to month 30
Mean Change in Fasting C-peptide Value, Month 43
Time frame: Baseline to month 43, extension period
Mean Change in HbA1c, Month 15
Time frame: Baseline to month 15
Mean Change in HbA1c, Month 30
Time frame: Baseline to month 30
Mean Change in HbA1c, Month 43
Time frame: Baseline to month 43, extension period
External Insulin Dose, Baseline
Time frame: Baseline
External Insulin Dose, Month 15
Time frame: Month 15
External Insulin Dose, Month 30
Time frame: Month 30
External Insulin Dose, Month 43
Time frame: Month 43, extension period
Mean IDAA1c Values, Baseline
Time frame: Baseline
Mean IDAA1c Values, Month 15
Time frame: Month 15
Mean IDAA1c Values, Month 30
Time frame: Month 30
Mean IDAA1c Values, Month 43
Time frame: Month 43, extension period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33162978Casas R, Dietrich F, Barcenilla H, Tavira B, Wahlberg J, Achenbach P, Ludvigsson J. Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients. Front Immunol. 2020 Oct 9;11:564921. doi: 10.3389/fimmu.2020.564921. eCollection 2020.
- Derived from this study: PubMed 30009185Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. J Diabetes Res. 2018 May 24;2018:9391845. doi: 10.1155/2018/9391845. eCollection 2018.
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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.
Johnny Ludvigsson, Professor principal investigator
Linkoeping University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GAD-Alum and Vitamin D in people with Diabetes Mellitus, Type 1, run by Johnny Ludvigsson 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 7 inclusion and 17 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 27 Apr 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Apr 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?
Number of Subjects With Injection Site Reactions Month 1 (time frame: Month 1). The study lists 4 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 NCT02352974, which also lists 2 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 27 Apr 2020.