L-glutamine has been approved in the US to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older. The purpose of this single-center, open-label, phase 4 study is to evaluate the pharmacokinetic characteristics and safety of L-glutamine in patients with SCD.
Sickle cell disease (SCD) is associated with a mutation in the β-hemoglobin gene that results in abnormal polymerization of hemoglobin. Polymerization of hemoglobin causes the red blood cell to sickle, leading to a cascade of events which cause acute complications for SCD patients. L-glutamine has been approved in the US to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older. The purpose of this single-center, open-label, phase 4 study is to evaluate the pharmacokinetic characteristics and safety of L-glutamine in patients with SCD. 8 SCD patients and 4 healthy volunteers will receive weight-based dosing of L-glutamine for 3 weeks. Doses will be changed weekly: 0.1 g/kg administered twice daily during week 1, 0.3 g/kg administered twice daily during week 2, and 0.6 g/kg administered once daily during week 3. The primary objective is to evaluate the pharmacokinetic characteristics of L-glutamine in SCD patients compared with healthy volunteers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
13
Pharmacokinetic study
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Area Under Curve (AUC) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
PK (AUC)
Time frame: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
Maximum Plasma Concentration (Cmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
PK (Cmax)
Time frame: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
Half-life (t1/2) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
PK (t1/2)
Time frame: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
Time to Peak Concentration (Tmax) of L-glutamine at 0.1 g/kg twice daily, 0.3 g/kg twice daily, and 0.6 g/kg once daily in SCD patients
PK (Tmax)
Time frame: Week 1 Day 1 (0.1 g/kg dose) and Week 2 Day 1 (0.3 g/kg dose. Week 3 Day 1 and Week4 Day1 (0.6 g/kg once daily dose)
Glutamate levels
Plasma and serum glutamate levels.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Effect of Food on L-glutamine Area Under Curve (AUC)
Food effect on AUC.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
Effect of Food on L-glutamine Maximum Plasma Concentration (Cmax)
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Food effect on Cmax.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 4 Day 1.
L-glutamine Dose Effect on Area Under Curve (AUC)
Dose effect on AUC.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
L-glutamine Dose Effect on Maximum Plasma Concentration (Cmax)
Dose effect on Cmax.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
L-glutamine Interpatient Variability of Area Under Curve (AUC)
Interpatient variability of AUC.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
L-glutamine Interpatient Variability of Maximum Plasma Concentration (Cmax)
Interpatient variability of Cmax.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.
Ammonia levels
Basal whole blood ammonia levels.
Time frame: Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, Week 4 Day 1.