E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients homozygous for sickle cell disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
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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 determine whether NAC therapy results in decreased red cell phosphatidylserine exposure, endothelial activation, inflammation, and reduction clotting activation in the steady state. We hypothesize that treatment of sickle cell patients with NAC results in reduced red cell phosphatidylserine exposure, reduced endothelial activation, increased NO availability, reduced coagulation activation and reduced inflammation detectable with specific laboratory testing, as well as a reduction of irreversibly sickled cells and Heinz Body formation
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E.2.2 | Secondary objectives of the trial |
Secondary outcome measures are tolerability of study medication at every visit by history taking and by scoring of a NAC for SCD check-list (see appendix B). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Ten patients with SCD (HbSS HbSC or HbSb) will be included. Inclusion criteria 1. High performance liquid chromatography confirmed diagnosis of HbSS HbSC or HbSb genotype 2. Aged 18-65 years 3. Written informed consent
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E.4 | Principal exclusion criteria |
Exclusion criteria 1. Bloodtransfusion in the preceding four months 2. Pregnancy or the desire to get pregnant in the following 7 months 3. Concommitant use of hydroxyurea, vitamin K antagonists or other oral anticoagulants, or contraindications for NAC. 4. Impaired renal function of more than 60% (as assessed by the Kockroft-Gauld equation) 5. Known gatsric or duodenal ulcer 6. Concomittant use of anti-hypertensives, sildefanil or nitrates.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measures are the effects of NAC on the laboratory markers described below. • hemoglobin levels, red blood cell counts, reticulocyte counts, leukocyte counts and differentiation, platelet counts, erythrocyte sedimentation rate will be determined with a automated cell counter. • A blood smear will be analyzed microscopically for the number of ISC per field, as well as the number of Heinz bodies • Intra-erythrocytic GSH and GSSG levels • NO availability (ratios of aminoacids involved in arginine metabolism) • SRBC PS exposure will be determined with flow cytometric quantification • Inflammation and endothelial activation (Serum levels of high sensitive CRP, sVCAM-1, ET-1, and IL-8) • Coagulation activation (pro-thrombin fragments (F1.2), D-dimer levels, protein S (free and total) and C activity, vWF-Ag activity)
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
before and after treatment baseline measurements |
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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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |