Sickle Cell Disease MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: ENDARI
Product Name: Endari
Pharmaceutical Form: Oral powder
Sponsors
Amsterdam UMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - High performance liquid chromatography (HPLC) conformed HbSS or HbSß0-thal - age 12 - 70 years - Able and willing to give informed consent - Good performance status (ECOG 0 or 1) Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: - Poor performance status (ECOG > 1) - HIV infection - Active acute infection - Inflammatory disease - Pregnancy - Blood cell transfusion within 4 months prior to screening - Vaso-occlusive painful crisis within 4 week prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of treatment with L-glutamine on sickling as evaluated by change in Point of Sicking (expressed in mmHg), as quantified by the Oxygenscan. Efficacy is defined as the lowest PoS measured during the treatment period relative (%) to the mean PoS at baseline (before treatment).;Secondary Objective: To evaluate the effect of L-glutamine treatment on: -Clinical characteristics such as fatigue and pain. -RBC degradation as expressed by phosphatidylserine (PS) exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes and hemoglobin -Oxidative stress as expressed by intracellular metabolomics and by plasma levels of AGEs -In vitro adhesion of RBCs to laminin -Endothelial activation as reflected by plasma levels of soluble vascular adhesion molecule-1 (sVCAM-1) and von Willebrand factor antigen (VWF:Ag) ;Primary end point(s): Efficacy is defined as the lowest PoS measured during the treatment period relative (%) to the mean PoS at baseline (before treatment). The primary endpoint of the study is the relative (percentage) decrease in PoS at 12 weeks of treatment as compared to baseline. ;Timepoint(s) of evaluation of this end point: baseline and after 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The absolute decrease in PoS at 12 weeks of treatment as compared to baseline. - Changes in daily (chronic) pain score (NRS) and frequency of pain at 12 weeks, compared to baseline - Changes in PS exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes) and hemoglobin at 12 weeks of treatment as compared to baseline. - Changes in oxidative stress (as expressed by intracellular metabolomics and by plasma levels of AGEs) after 12 weeks of treatment as compared to baseline. - Changes in in vitro adhesion of RBCs to laminin after 12 weeks of treatment as compared to baseline. - Changes in plasma levels of sVCAM-1 and VWF:Ag (as markers of endothelial activation) at 12 weeks of treatment compared to baseline. ;Timepoint(s) of evaluation of this end point: baseline and after 12 weeks of treatment | — |
Countries
Netherlands
Contacts
Public ContactTrialbureau Hematology
Amsterdam UMC
Outcome results
None listed