E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Beta-cell function in C-peptide positive type 1 diabetes |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of 52 weeks of treatment with liraglutide 1.8 mg/day, compared to placebo, on stimulated C-peptide concentrations in patients with long-standing type 1 diabetes (T1D) and residual insulin production. |
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E.2.2 | Secondary objectives of the trial |
To study changes in metabolic control, Quality of Life (QoL), and humoral and cellular immunity during the year of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent for participation of the study, given before undergoing any study-specific procedures. • 18-30 years of age (age interval inclusive of both the ends). Both males and females are eligible for the study • Clinical diagnose of T1D • 5 or more years duration of disease • HbA1C between 45 and 75 mmol/mol • Fasting plasma C-peptide concentration >1.5 pmol/l. |
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E.4 | Principal exclusion criteria |
• Inability to provide informed consent • Mental incapacity • Unwillingness or language barrier precluding adequate understanding or cooperation • Ongoing or planned pregnancy within the next 12 months • Inadequate or no use of contraceptives • Ongoing breast feeding • Known sight-threatening retinopathy • Creatinine clearance <60 ml/min • Life-threatening cardiovascular disease • History of drug/alcohol abuse • Known or suspected allergy to trial product or related product • Recurrent assisted hypoglycemias • Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin • Uncontrolled hypertension (180/105 mmHg or above) • History of acute or chronic pancreatitis • Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) • Personal history of non-familial medullary thyroid carcinoma. • Any condition that the investigator or sponsor feel would interfere with trial participation or evaluation of results
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy end-point will be ∆-change in C-peptide AUC between the MMTT after one year and that after the run-in period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.∆- change in C-peptide AUC between the MMTT after one year and that after 6 weeks of treatment 2. ∆-change in C-peptide AUC between the MMTT three months after cessation of treatment and that after the run-in period 3. ∆- change in HbA1c between after one year and after the run-in period. 4. ∆- change in HbA1c between after one year and after 6 weeks of treatment 5. ∆- change in HbA1c between three months after the cessation of treatment and after the run-in period. 6. ∆- change in exogenous insulin doses between after one year and after the run-in period. 7. ∆- change in exogenous insulin doses between after one year and after 6 weeks of treatment 8. ∆- change in exogenous insulin doses between three months after the cessation of treatment and after the run-in period. 9. ∆- change in glucose variability between after one year and after the run-in period. 10. ∆- change in glucose variability between after one year and after 6 weeks of treatment 11. ∆- change in glucose variability between three months after the cessation of treatment and after the run-in period. 12. ∆- change in hypoglycemia frequency (measured plasma glucose levels < 3 mmol/l or assisted hypoglycemia during a one week period) between one year and after the run-in period. 13. ∆- change in hypoglycemia frequency (measured plasma glucose levels < 3 mmol/l or assisted hypoglycemia during a one week period) after one year and after 6 weeks of treatment 14. ∆- change in hypoglycemia frequency (measured plasma glucose levels < 3 mmol/l or assisted hypoglycemia during a one week period) between three months after the cessation of treatment and after the run-in period. 15. ∆- change in assessment of QoL between after one year and after the run-in period. 16. ∆- change in assessment of QoL between after one year and after 6 weeks of treatment 17. ∆- change in assessment of QoL between three months after the cessation of treatment and after the run-in period.
Explorative endpoints 1. ∆- change in presence of islet autoantibodies (GAD, IA2) in plasma between after one year and after the run-in period. 2. ∆- change in presence of islet autoantibodies (GAD, IA2) in plasma between after one year and after 6 weeks of treatment. 3. ∆- change in presence of islet autoantibodies (GAD, IA2) in plasma between 3 months after cessation of treatment and after the run-in period. 4. ∆- change in circulating levels of cytokines (IL-2, IL-6, IL-10, IL-17, IL-21, IL-33, IL-35, IFN-gamma and TGF-beta) in plasma between after one year and after the run-in period. 5. ∆- change in circulating levels of cytokines (IL-2, IL-6, IL-10, IL-17, IL-21, IL-33, IL-35, IFN-gamma and TGF-beta) in plasma between after one year and after 6 weeks of treatment. 6. ∆- change in circulating levels of cytokines (IL-2, IL-6, IL-10, IL-17, IL-21, IL-33, IL-35, IFN-gamma and TGF-beta) in plasma between 3 months after cessation of treatment and after the run-in period. 7. ∆- change in the proportion of different immune cells such as; antigen presenting cells, T-cells, regulatory T cells, regulatory B cells and other innate immune cells in plasma between after one year and after the run-in period 8. ∆- change in the proportion of different immune cells such as; antigen presenting cells, T-cells, regulatory T cells, regulatory B cells and other innate immune cells in plasma between after one year and after 6 weeks of treatment. 9. ∆- change in the proportion of different immune cells such as; antigen presenting cells, T-cells, regulatory T cells, regulatory B cells and other innate immune cells in plasma between 3 months after cessation of treatment and after the run-in period. 10. ∆- change in PBMC immune regulatory genes expression between after one year and after the run-in period 11. ∆- change in PBMC immune regulatory genes expression between after one year and after 6 weeks of treatment. 12. ∆- change in PBMC immune regulatory genes expression between 3 months after cessation of treatment and after the run-in period. 13. ∆- change in unmethylated INS DNA between after one year and after the run-in period. 14. ∆- change in unmethylated INS DNA between after one year and after 6 weeks of treatment. 15. ∆- change in unmethylated INS DNA between 3 months after cessation of treatment and after the run-in period.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After run-in, at 6 weeks and one year of treatment and at three months after cessation of treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Possibility to increase residual insulin production measured as C-peptide in long-standing type 1 diabetes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |