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

Tracking Information
First Submitted Date ICMJE	May 21, 2010
First Posted Date ICMJE	August 11, 2010
Results First Submitted Date	December 14, 2016
Results First Posted Date	August 10, 2017
Last Update Posted Date	August 10, 2017
Study Start Date ICMJE	May 2010
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 9, 2010)	The Number of Occurrences of Sickle Cell Crises [ Time Frame: 48 weeks ]; The number of occurrences of protocol-defined sickle cell crises that occur from 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.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01179217 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 8, 2017)	The Number of Hospitalizations for Sickle Cell Pain [ Time Frame: 48 weeks ]The number of hospitalizations that occur from 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.; The Number of Emergency Room/Medical Facility Visits for Sickle Cell Pain [ Time Frame: 48 weeks ]The number of emergency room visits or medical facility visits that occur from 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.; The Effect of Oral -L-glutamine on Hematological Parameters [ Time Frame: Baseline, Week 4, 24 and 48 ]To assess the effect of oral L-glutamine on hematological parameters (hemoglobin), Change from Baseline will be reported at Weeks 4, 24 and 48.; The Effect of Oral L-glutamine on Vital Signs [ Time Frame: Baseline, Week 4, 24, and 48 ]To assess the effect of oral L-glutamine on Vital signs (systolic and diastolic blood pressure). Change from Baseline will be reported at Weeks 4, 24, and 48.; The Effect of Oral L-glutamine on Hematological Parameters [ Time Frame: Baseline, Week 4, 24 and 48 ]To assess the effect of oral L-glutamine on hematological parameters (hematocrit), Change from Baseline will be reported at Weeks 4, 24 and 48.; The Effect of Oral L-glutamine on Hematological Parameters [ Time Frame: Baseline, Week 4, 24 and 48 ]To assess the effect of oral L-glutamine on hematological parameters (reticulocyte count), Change from Baseline will be reported at Weeks 4, 24 and 48.; The Effect of Oral L-glutamine on Vital Signs [ Time Frame: Baseline, Week 4, Week 24 and Week 48 ]To assess the effect of oral L-glutamine on Vital signs (pulse rate). Change from Baseline will be reported at Weeks 4, 24, and 48.; Effect of Oral L-glutamine on Vital Signs [ Time Frame: Baseline, Week 4, Week 24 and Week 48 ]To assess the effect of oral L-glutamine on Vital signs (temperature). Change from Baseline will be reported at Weeks 4, 24, and 48.; The Effect of Oral L-glutamine on Vital Signs [ Time Frame: Baseline, Week 4, Week 24 and Week 48 ]To assess the effect of oral L-glutamine on Vital signs (respiration). Change from Baseline will be reported at Weeks 4, 24, and 48.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
Official Title ICMJE	A PHASE III, PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER STUDY OF L GLUTAMINE THERAPY FOR SICKLE CELL ANEMIA AND SICKLE ß0-THALASSEMIA
Brief Summary	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.
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Sickle Cell Anemia; Sickle ß0-Thalassemia
Intervention ICMJE	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. Other Name: oral L-glutamine; Drug: Placebo 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. Other Name: Maltodextrin
Study Arms	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: Placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 24, 2014)	230
Original Estimated Enrollment ICMJE; (submitted: August 9, 2010)	225
Actual Study Completion Date	March 2014
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	5 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01179217
Other Study ID Numbers ICMJE	GLUSCC09-01
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: Undecided
Responsible Party	Emmaus Medical, Inc.
Study Sponsor ICMJE	Emmaus Medical, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Yutaka Niihara, MD, MPH Chairman and CEO
PRS Account	Emmaus Medical, Inc.
Verification Date	July 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP