A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia

• The number of occurrences of sickle cell crises [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  The number of occurrences of protocol-defined sickle cell crises that occur from Week 0 to Week 24 will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
• Number of hospitalizations for sickle cell pain [ Time Frame: 24 weeks; 48 weeks ] [ Designated as safety issue: No ]
  The number of hospitalizations that occur from Week 0 to Week 24, and Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
• Number of emergency room/medical facility visits for sickle cell pain [ Time Frame: 24 weeks; 48 weeks ] [ Designated as safety issue: No ]
  The number of emergency room visits or medical facility visits that occur from Week 0 to Week 24, and Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
• Hematological parameters [ Time Frame: 24 weeks; 48 weeks ] [ Designated as safety issue: No ]
  Change from Baseline (Week 0) for hemoglobin, hematocrit, reticulocyte count will be assessed at 24 weeks and 48 weeks to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
• Adverse events [ Time Frame: Week 0 - study exit ] [ Designated as safety issue: Yes ]
  All adverse events that occur between Baseline (Week 0) and the completion of study participation will be documented.
• Laboratory parameters and vital signs [ Time Frame: Screening through study exit ] [ Designated as safety issue: Yes ]
  Complete Blood Count (CBC) and reticulocyte count will be collected at Screening, Baseline, and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and 53. Serum chemistry and hepatic panel will be collected at Screening and at study exit. Vital signs will be recorded at each study visit.

• Sickle Cell Anemia
• Sickle ß0-Thalassemia

• Drug: L-glutamine
  0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.
• Drug: 100% maltodextrin
  0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

• Experimental: L-glutamine
  Patients will be randomized to receive investigational product, L-Glutamine.
  Intervention: Drug: L-glutamine
• Placebo Comparator: 100% maltodextrin
  Patients will be randomized to receive Placebo.
  Intervention: Drug: 100% maltodextrin

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 (refer to Appendix 3 for guidelines).
• 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.