E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study will investigate the effect of deferoxamine on the impaired reaction to hypoxia in patients with diabetes mellitus type 1. |
|
E.1.1.1 | Medical condition in easily understood language |
The study will investigate the effect of deferoxamine on the impaired reaction to oxygen deficiency in patients with diabetes. |
|
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 whether systemic administration of deferoxamine can reverse the impaired response to hypoxic challenge in patients with diabetes mellitus type 1. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients with diabetes mellitus type 1 with a duration of the disease between 10 and 20 years
•HbA1c 55-100 mmol/mol
•Age 18-55
•Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal (and not surgically sterile), be prepared to use ≥1 effective method of contraception during the study and for 30 days after the last visit. Effective methods of contraception are considered to be those listed below: Double barrier method, i.e. (a) condom (male or female) or (b) diaphragm, with spermicide; or Intrauterine device; or Vasectomy (partner); or Hormonal (e.g. contraceptive pill, patch, intramuscular implant or injection); or Abstinence, if in line with the preferred and usual lifestyle of the subject.
•Signed informed consent
|
|
E.4 | Principal exclusion criteria |
•Major cardiovascular complications such as coronary heart disease, unstable or stable angina, myocardial infarction, ventricular arrhythmias, and atrial fibrillation in the last 3 months
•Decompensated congestive heart failure of functional class 3-4.
•Therapy with β-blockers
•Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic blood pressure)
•Proliferative retinopathy
•Sign for peripheric diabetic neuropathy (decreased/absent sensitivity to 10 g monofilament, vibration, plantar reflex)
•Definite autonomic dysfunction
•History of anemia, bleeding gastric ulcer, abundant menstruation
•Currently smoking
•History of alcohol or drug abuse
•Infections during the last month
•Malignancy
•Participant in another ongoing pharmacological study
•Unwillingness to participate following oral and written information
•If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
•Any concomitant disease or condition that may interfere with the possibility for the subject to comply with or complete the study protocol
•Subjects with any other severe acute or chronic medical or psychiatric condition that make the subject inappropriate for the study in the judgment of the Investigator
•Treatment with Prochlorperazine
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Endothelial Precursor Cells number increase after intermittent hypoxia exposure |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 hours after intermittent hypoxia exposure compared to baseline |
|
E.5.2 | Secondary end point(s) |
1. Changes in the levels of angiogenetic chemokines (SDF-1, EPO, VEGF)
2. Changes in the levels of angiogenetic and hypoxic induced genes (VEGFA, SDF-1, BPNP3, GLUT3, PDK1)
3. Changes in electrophysiological parameters important for the cardiorespiratory response:
o R-R interval change
o the standard deviation of the R-R interval (SDNN)
o systolic and diastolic blood pressure
o end-tidal carbon dioxide (CO2-et)
o arterial oxygen saturation (SaO2)
o breathing rate
o tidal volume (Vt), minute ventilation (VE), and the ratio between Vt and inspiration time (Vt/Ti)
o baroreflex sensitivity (BRS)
o arterial function parameters: pulse wave velocity, augmentation index (AI), augmentation index corrected for heart rate (AI75)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 6 hours after intermittent hypoxia exposure compared to baseline
2. 3 and 6 hours after intermittent hypoxia exposure compared to baseline
3. Immediately after and 3 and 6 hours after intermittent hypoxia exposure compared to baseline |
|
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 | Yes |
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 | 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 | 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 | No |
E.8.1.6 | Cross over | Yes |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |