A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for
 Sickle Cell Anemia or Sickle ß0 Thalassemia as evaluated by the number of occurrences of
 sickle cell crises.
Primary objective:

 To evaluate the efficacy of oral L-glutamine as a therapy for sickle cell anemia and sickle
 ß0-thalassemia as evaluated by the number of occurrences of sickle cell crises.

 Secondary objectives:

 To assess the effect of oral L-glutamine on: (a) frequency of hospitalizations for sickle
 cell pain; (b) frequency of emergency room/medical facility visits for sickle cell pain; and
 (c) hematological parameters (hemoglobin, hematocrit, and reticulocyte count); and to assess
 the safety of L-glutamine as a therapy for sickle cell anemia as evaluated by adverse events,
 laboratory parameters, and vital signs.

 Methodology:

 This was a 2:1 randomized, double-blind, placebo-controlled, parallel-group, multicenter
 study in patients with sickle cell anemia and sickle ß0-thalassemia who were at least 5 years
 old. Informed consent was obtained up to four weeks prior to Week 0 (Baseline). Screening
 procedures were performed anytime between the date of consent and Week 0, as long as all
 eligibility criteria had been confirmed prior to Week 0. At Week 0, patients were randomized
 (to L-glutamine or placebo) and underwent 48 weeks of treatment (orally BID), with dose
 calculated according to patient weight. Patient clinic visits occurred every 4 weeks, and
 phone calls took place between visits to monitor compliance. After 48 weeks of treatment, the
 dose was tapered to 0 within 3 weeks. A final evaluation visit occurred 2 weeks after last
 dose for a total of 53 weeks on study.
Inclusion Criteria:

 -  Patient is at least five years of age.

 -  Patient has been diagnosed with sickle cell anemia or sickle ß°-thalassemia
 (documented by hemoglobin electrophoresis).

 -  Patient has had at least two documented episodes of sickle cell crises within 12
 months of the screening visit.

 -  If the patient has been treated with an anti-sickling agent within three months of the
 screening visit, the therapy must have been continuous for at least three months with
 the intent to continue for the duration of the study.

 -  Patient or the patient's legally authorized representative has given written informed
 consent.

 -  If the patient is a female of child-bearing potential, she agrees to avoid pregnancy
 during the study and is willing and agrees to practice a recognized form of birth
 control during the course of the study (e.g. barrier, birth control pills,
 abstinence).

 Exclusion Criteria:

 -  Patient has a significant medical condition that required hospitalization (other than
 sickle cell crisis) within two months of the screening visit.

 -  Patient has prothrombin time INR > 2.0.

 -  Patient has serum albumin < 3.0 g/dl.

 -  Patient has received any blood products within three weeks of the Screening Visit.

 -  Patient has uncontrolled liver disease or renal insufficiency.

 -  Patient is pregnant or lactating or has the intention of becoming pregnant during the
 study (if female and of child-bearing potential).

 -  Patient is currently taking or has been treated with any form of glutamine supplement
 within 30 days of the screening visit.

 -  Patient has been treated with an experimental anti-sickling medication/ treatment
 within 30 days of the screening visit (with the exception of hydroxyurea in pediatric
 patients).

 -  Patient is currently taking or has been treated with an investigational drug within 30
 days of the screening visit (with the exception of hydroxyurea in pediatric patients).

 -  Patient is currently enrolled in an investigational drug or device study and/or has
 participated in such a study within 30 days of the screening visit.

 -  There are factors that would, in the judgment of the investigator, make it difficult
 for the patient to comply with the requirements of the study.