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

Phase 3

Completed

Conditions: Sickle Cell Anemia
Sickle ß0-Thalassemia

Interventions: Drug: Placebo
Drug: L-glutamine

Registration Number: NCT01179217

Lead Sponsor: Emmaus Medical, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 230

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
100% maltodextrin	Placebo	Patients will be randomized to receive Placebo.
L-glutamine	L-glutamine	Patients will be randomized to receive investigational product, L-Glutamine.

Primary Outcome Measures

Name	Time	Method
The Number of Occurrences of Sickle Cell Crises	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.

Secondary Outcome Measures

Name	Time	Method
The Effect of Oral -L-glutamine on Hematological Parameters	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 Hematological Parameters	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	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.
The Number of Hospitalizations for Sickle Cell Pain	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	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.
Effect of Oral L-glutamine on Vital Signs	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.

Trial Locations

Locations (31): Howard University Hospital & Howard University
🇺🇸
Washington, District of Columbia, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
Interfaith Medical Center
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Brooklyn, New York, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Bronx Lebanon Hospital
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Bronx, New York, United States
University of Illinois at Chicago
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Chicago, Illinois, United States
University of Louisville School of Medicine
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Louisville, Kentucky, United States
Children's Mercy Hospitals and Clinics
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Kansas City, Missouri, United States
SUNY - Downstate Medical Center
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Brooklyn, New York, United States
Comprehensive Cancer Center of Nevada
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Las Vegas, Nevada, United States
Phoenix Children's Hospital Center for Cancer and Blood Disorders
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Phoenix, Arizona, United States
Children's Hospital of Michigan
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Detroit, Michigan, United States
University of South Alabama Medical Center
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Mobile, Alabama, United States
Children's Hospital & Research Center at Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente
🇺🇸
Inglewood, California, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Harbor-UCLA Medical Center
🇺🇸
Torrance, California, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta at Egleston/Emory University
🇺🇸
Atlanta, Georgia, United States
Sickle Cell Center of S. Louisiana, Tulane University School of Medicine
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New Orleans, Louisiana, United States
Children's Specialty Center of Nevada
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Las Vegas, Nevada, United States
Boston University Medical Center
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Boston, Massachusetts, United States
University of Mississippi Medical Center
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Jackson, Mississippi, United States
Cooper University Hospital
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Camden, New Jersey, United States
The Brooklyn Hospital Center
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Brooklyn, New York, United States
New York Methodist Hospital - SC/Thalassemia Program
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Brooklyn, New York, United States
Brookdale University Hospital and Medical Center
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Brooklyn, New York, United States
Presbyterian Blume Pediatric Hematology-Oncology Clinic
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Charlotte, North Carolina, United States
Virginia Commonwealth University
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Richmond, Virginia, United States
University of Tennessee Cancer Institute
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Memphis, Tennessee, United States
University of Denver School of Medicine Sickle Cell Treatment & Research Center
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Aurora, Colorado, United States