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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002692-34 | EudraCT Number |
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| Name | Class |
|---|---|
| St. Olavs Hospital | OTHER |
| Diamyd Medical AB | INDUSTRY |
| Karolinska Institutet | OTHER |
| Linkoeping University |
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This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production.
The purpose of the trial is to evaluate the effects of 3 intra-nodal injections of GAD-alum, together with oral vitamin D supplementation, in a population of LADA patients with high GADA titers. Effects will be summarized at 5 and 12 months after the first injection.
The study is an open label Phase IIa feasibility trial. It is a pilot study that does not include a placebo arm.
Antidiabetic medication in the form of metformin is acceptable before and during the trial. Study participants must be insulin independent at baseline, but if the need for insulin treatment develops during the trial, such treatment will be given.
GAD-alum will be injected directly into an inguinal lymph node by a qualified radiologist.
Patients will be followed for a total of 12 months during which their endogenous insulin production and immune response will be evaluated at regular intervals throughout the study period. Urine and blood samples will be taken for safety, diabetes status assessments, vitamin D levels and immunological assessments. Concomitant medication and demographics will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GAD-vaccination with vitamin D suppletion | Experimental | Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel | Drug | 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden |
| Measure | Description | Time Frame |
|---|---|---|
| Injection Site Skin Reactions | Injection site skin reactions 1 hour post injection, i.e., erythema, oedema, haematoa, tenderness, pain, itching or other finding. | 1 hour |
| Occurrence of Adverse Events (AEs) During 5 Months From Baseline. | AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized. | From baseline (first injection of GAD-alum) to 5 months after baseline. |
| Occurrence of Adverse Events (AEs) During the Study. | AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit/first injection of GAD-alum). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized. | From baseline (first injection of GAD-alum) to 12 months after baseline. |
| Serum GAD65A Titers, Change From Baseline at 5 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline. | Baseline (first injection of GAD-alum) and 5 months after baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Secretion, Change From Baseline to 5 Months After Baseline. | Values present changes in serum values of glucagon-stimulated C-peptide from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline. | Baseline (first injection of GAD-alum) and 5 months after baseline. |
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Inclusion Criteria:
Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows:
For females of childbearing potential:
For males of childbearing potential:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne Hildur Henriksen, MD PhD | St Olavs Hospital, Medisinsk Klinikk | Study Director |
| Torstein Baade Rø, MD | Norwegian University of Science and Technology, IKOM | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Endocrinology, St Olavs Hospital | Trondheim | Norway | ||||
| Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31148332 | Background | Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Bjorklund A. Investigating optimal beta-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019 Oct;21(10):2219-2227. doi: 10.1111/dom.13797. Epub 2019 Jun 19. |
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There is not a plan to make IPD available.
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| ID | Title | Description |
|---|---|---|
| FG000 | GAD-vaccination With Vitamin D Suppletion | Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total). recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel: 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden Vitamin D: 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GAD-vaccination With Vitamin D Suppletion | Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total). recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel: 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden Vitamin D: 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Injection Site Skin Reactions | Injection site skin reactions 1 hour post injection, i.e., erythema, oedema, haematoa, tenderness, pain, itching or other finding. | All study participants received 3 injections of 4 µg GAD-alum. | Posted | Number | events | 1 hour |
|
One year. AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit/first injection of GAD-alum).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GAD-vaccination With Vitamin D Suppletion | Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart. Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total). recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel: 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden Vitamin D: 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA Version 26.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ingrid K Hals | NTNU | +47 73412207 | ingrid.hals@ntnu.no |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 29, 2021 | Sep 2, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000071698 | Latent Autoimmune Diabetes in Adults |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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| OTHER_GOV |
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|
| Vitamin D | Drug | 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden |
|
|
| Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. | Baseline and 12 months after baseline. |
| Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. | Baseline (first injection of GAD-alum) and 12 months after baseline. |
| Insulin Secretion, Change From Baseline to 12 Months After Baseline. |
Values present changes in serum values of glucagon-stimulated C-peptide from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. |
| Baseline (first injection of GAD-alum) and 12 months after baseline. |
| Change in HbA1c | HbA1c at 12 months vs. baseline (first injection) | from baseline to 12 months after the first injection |
| Change in Fasting Glucose | Change in fasting glucose at 12 months vs baseline (first injection) | From baseline to 12 months after the first injection |
| Change in Fasting C-peptide | Change in fasting glucose at 12 months vs baseline (first injection) | Between baseline and 12 months after the first injection |
| Change in Maximum C-peptide During Mixed Meal Tolerance Test (MMTT) | Change in maximum C-peptide value at 12 months vs baseline (first injection) | between baseline 12 months after the first injection |
| Stockholm |
| Sweden |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Time from diagnosis to inclusion, months | Median | Full Range | months |
|
| BMI, kg/m^2 | Median | Full Range | kg/m^2 |
|
| Fasting C-peptide, nmol/L | Median | Full Range | nmol/L |
|
| Fasting glucose, mmol/L | Median | Full Range | mmol/L |
|
| HbA1c, mmol/mol | Median | Full Range | mmol/mol |
|
|
|
| Primary | Occurrence of Adverse Events (AEs) During 5 Months From Baseline. | AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized. | Posted | Number | AEs | From baseline (first injection of GAD-alum) to 5 months after baseline. |
|
|
|
|
| Primary | Occurrence of Adverse Events (AEs) During the Study. | AEs were continuously monitored and registered from the baseline visit (first injection of GAD-alum) to the end of study (12 months after the baseline visit/first injection of GAD-alum). The total number of AEs registered for all 14 participants during the first 5 months from baseline was summarized when all 14 participants had completed their 5 months study visit (i.e., 5 months after the baseline visit). At the end of study, when all 14 participants had completed their 12 months study visit, the total number of AEs registered for all 14 participants during the 12 months from baseline was summarized. | Posted | Number | AEs | From baseline (first injection of GAD-alum) to 12 months after baseline. |
|
|
|
|
| Primary | Serum GAD65A Titers, Change From Baseline at 5 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline. | Posted | Median | Full Range | U/mL | Baseline (first injection of GAD-alum) and 5 months after baseline. |
|
|
|
|
| Primary | Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. | Posted | Median | Full Range | U/mL | Baseline and 12 months after baseline. |
|
|
|
|
| Secondary | Insulin Secretion, Change From Baseline to 5 Months After Baseline. | Values present changes in serum values of glucagon-stimulated C-peptide from baseline (first injection of GAD-alum) to 5 months after baseline. Calculation: Value at 5 months minus value at baseline. | Posted | Median | Full Range | nmol/L | Baseline (first injection of GAD-alum) and 5 months after baseline. |
|
|
|
|
| Secondary | Insulin Secretion, Change From Baseline to 12 Months After Baseline. | Values present changes in serum values of glucagon-stimulated C-peptide from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. | Posted | Median | Full Range | nmol/L | Baseline (first injection of GAD-alum) and 12 months after baseline. |
|
|
|
|
| Secondary | Change in HbA1c | HbA1c at 12 months vs. baseline (first injection) | Posted | Median | Full Range | mmol/mol | from baseline to 12 months after the first injection |
|
|
|
|
| Secondary | Change in Fasting Glucose | Change in fasting glucose at 12 months vs baseline (first injection) | Posted | Median | Full Range | mmol/L | From baseline to 12 months after the first injection |
|
|
|
|
| Secondary | Change in Fasting C-peptide | Change in fasting glucose at 12 months vs baseline (first injection) | Posted | Median | Full Range | nmol/L | Between baseline and 12 months after the first injection |
|
|
|
|
| Secondary | Change in Maximum C-peptide During Mixed Meal Tolerance Test (MMTT) | Change in maximum C-peptide value at 12 months vs baseline (first injection) | Posted | Median | Full Range | nmol/L | between baseline 12 months after the first injection |
|
|
|
|
| Primary | Serum GAD65A Titers, Change From Baseline at 12 Months After Baseline. | Values present changes in serum GAD65A titers from baseline (first injection of GAD-alum) to 12 months after baseline. Calculation: Value at 12 months minus value at baseline. | Posted | Median | Full Range | U/mL | Baseline (first injection of GAD-alum) and 12 months after baseline. |
|
|
|
| 0 |
| 14 |
| 2 |
| 14 |
| 12 |
| 14 |
| Muscle rupture | Injury, poisoning and procedural complications | MedDRA Version 26.0 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| Vertigo or vertigo positional | Ear and labyrinth disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| diarrhoea | Gastrointestinal disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| Pancreatic cystadenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 26.0 | Non-systematic Assessment |
|
| General disorders and administration site conditions | General disorders | MedDRA Version 26.0 | Non-systematic Assessment | Chest pain, injection site erythema or haemorrhage or pain, pyrexia, |
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| Biliary colic | Hepatobiliary disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| COVID-19, nasopharyngitis, upper respiratory tract infection | Infections and infestations | MedDRA Version 26.0 | Non-systematic Assessment |
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| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA Version 26.0 | Non-systematic Assessment |
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| Wrong product administered | Injury, poisoning and procedural complications | MedDRA Version 26.0 | Non-systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA Version 26.0 | Non-systematic Assessment |
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| Blood urine present | Investigations | MedDRA Version 26.0 | Non-systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| Nasal congestion and throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 26.0 | Non-systematic Assessment |
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| Menopause | Social circumstances | MedDRA Version 26.0 | Non-systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |