E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Immune System Diseases [C20] |
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 compare pancreatic macrophage infiltration between individuals with T1D and controls by imaging intracellular iron particle accumulation in macrophages by late-phase MR imaging. To achieve this we will first develop an optimized nano-MRI protocol in 5 healthy volunteers. |
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E.2.2 | Secondary objectives of the trial |
• Compare pancreatic perfusion between individuals with T1D and non-diabetic control individuals by MR imaging of the angiographic phase after iron particle contrast infusion (comparing baseline perfusion and perfusion upon stimulation of pancreatic islets by glucose).
• Compare nano-MRI with quantitative dynamic [18F]FDG PET/CT to cross-validate the potential of nano-MRI to determine pancreatic inflammation.
• Correlate pancreatic macrophage infiltration to (residual) beta cell function assessed by oral glucose tolerance test and arginine stimulation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Inclusion criteria (Individuals with type 1 diabetes):
Within 6 months of diagnosis with type 1 diabetes
Auto-antibody positive
- Inclusion criteria (Control individuals):
No evidence of impaired glucose tolerance (HbA1c < 42 mmol/mol (6%), fasting glucose < 6.1 mmol/L)
- Inclusion criteria (general):
Age > 18 years
Signed informed consent
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E.4 | Principal exclusion criteria |
- Contra-indication to MRI scanning, iron infusion or hypersensitivity to the active substance or any of the excipients (like mentioned in the SPC).
- Known drug allergies or history of sever asthma, eczema or other ectopic allergies.
- Inability to lie still for at least 30 minutes or comply with imaging
- Hemochromatosis or liver disease defined as ALAT or ASAT level of more than three times the upper limit of normal range
- Renal dysfunction defined as MDRD < 40 ml/min/1.73m2
- Current pregnancy or the wish to become pregnant within 2 months
- Breast feeding
- Incapability to provide informed consent
- Pancreatitis
- Evidence of other inflammatory disease(s)
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E.5 End points |
E.5.1 | Primary end point(s) |
The main parameter of the study is the comparison of macrophage infiltration between individuals with T1D and controls. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After inclusion of all patients |
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E.5.2 | Secondary end point(s) |
o Comparison of pancreatic perfusion between individuals with T1D and controls
o Comparison of nano-MRI with [18F]FDG PET/CT for cross-validation of the potential of nano-MRI to determine pancreatic inflammation
o Correlation of pancreatic macrophage infiltration to (residual) beta cell function
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After inclusion of all patients |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |