Back to resultsA Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
Primary Purpose
Sickle Cell Anemia, Sickle ß0-Thalassemia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
L-glutamine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Anemia focused on measuring Sickle Cell Anemia, Sickle Cell Pain Crises, Painful Crises, Sickle Cell Pain, Vaso-occlusive Crises
Eligibility Criteria
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.
Sites / Locations
- University of South Alabama Medical Center
- Phoenix Children's Hospital Center for Cancer and Blood Disorders
- Kaiser Permanente
- Children's Hospital & Research Center at Oakland
- Children's Hospital of Orange County
- Harbor-UCLA Medical Center
- University of Denver School of Medicine Sickle Cell Treatment & Research Center
- Howard University Hospital & Howard University
- University of Florida
- All Children's Hospital
- Children's Healthcare of Atlanta at Egleston/Emory University
- University of Illinois at Chicago
- University of Louisville School of Medicine
- Sickle Cell Center of S. Louisiana, Tulane University School of Medicine
- Johns Hopkins University
- Boston University Medical Center
- Children's Hospital of Michigan
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Children's Specialty Center of Nevada
- Comprehensive Cancer Center of Nevada
- Cooper University Hospital
- Bronx Lebanon Hospital
- The Brooklyn Hospital Center
- SUNY - Downstate Medical Center
- Brookdale University Hospital and Medical Center
- New York Methodist Hospital - SC/Thalassemia Program
- Interfaith Medical Center
- Presbyterian Blume Pediatric Hematology-Oncology Clinic
- University of Tennessee Cancer Institute
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
L-glutamine
100% maltodextrin
Arm Description
Patients will be randomized to receive investigational product, L-Glutamine.
Patients will be randomized to receive Placebo.
Outcomes
Primary Outcome Measures
The Number of Occurrences of Sickle Cell Crises
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
The Number of Hospitalizations for Sickle Cell Pain
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
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
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
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
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
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
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
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
To assess the effect of oral L-glutamine on Vital signs (respiration). Change from Baseline will be reported at Weeks 4, 24, and 48.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01179217
Brief Title
A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emmaus Medical, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Anemia, Sickle ß0-Thalassemia
Keywords
Sickle Cell Anemia, Sickle Cell Pain Crises, Painful Crises, Sickle Cell Pain, Vaso-occlusive Crises
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
230 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-glutamine
Arm Type
Experimental
Arm Description
Patients will be randomized to receive investigational product, L-Glutamine.
Arm Title
100% maltodextrin
Arm Type
Placebo Comparator
Arm Description
Patients will be randomized to receive Placebo.
Intervention Type
Drug
Intervention Name(s)
L-glutamine
Other Intervention Name(s)
oral L-glutamine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Maltodextrin
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Number of Occurrences of Sickle Cell Crises
Description
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.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
The Number of Hospitalizations for Sickle Cell Pain
Description
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.
Time Frame
48 weeks
Title
The Number of Emergency Room/Medical Facility Visits for Sickle Cell Pain
Description
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.
Time Frame
48 weeks
Title
The Effect of Oral -L-glutamine on Hematological Parameters
Description
To assess the effect of oral L-glutamine on hematological parameters (hemoglobin), Change from Baseline will be reported at Weeks 4, 24 and 48.
Time Frame
Baseline, Week 4, 24 and 48
Title
The Effect of Oral L-glutamine on Vital Signs
Description
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.
Time Frame
Baseline, Week 4, 24, and 48
Title
The Effect of Oral L-glutamine on Hematological Parameters
Description
To assess the effect of oral L-glutamine on hematological parameters (hematocrit), Change from Baseline will be reported at Weeks 4, 24 and 48.
Time Frame
Baseline, Week 4, 24 and 48
Title
The Effect of Oral L-glutamine on Hematological Parameters
Description
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.
Time Frame
Baseline, Week 4, 24 and 48
Title
The Effect of Oral L-glutamine on Vital Signs
Description
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.
Time Frame
Baseline, Week 4, Week 24 and Week 48
Title
Effect of Oral L-glutamine on Vital Signs
Description
To assess the effect of oral L-glutamine on Vital signs (temperature). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame
Baseline, Week 4, Week 24 and Week 48
Title
The Effect of Oral L-glutamine on Vital Signs
Description
To assess the effect of oral L-glutamine on Vital signs (respiration). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame
Baseline, Week 4, Week 24 and Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yutaka Niihara, MD, MPH
Organizational Affiliation
Chairman and CEO
Official's Role
Study Director
Facility Information:
Facility Name
University of South Alabama Medical Center
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36617
Country
United States
Facility Name
Phoenix Children's Hospital Center for Cancer and Blood Disorders
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Kaiser Permanente
City
Inglewood
State/Province
California
ZIP/Postal Code
90301
Country
United States
Facility Name
Children's Hospital & Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
University of Denver School of Medicine Sickle Cell Treatment & Research Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Howard University Hospital & Howard University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20060
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0296
Country
United States
Facility Name
All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Children's Healthcare of Atlanta at Egleston/Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Louisville School of Medicine
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Sickle Cell Center of S. Louisiana, Tulane University School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Children's Specialty Center of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Comprehensive Cancer Center of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Bronx Lebanon Hospital
City
Bronx
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
The Brooklyn Hospital Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
SUNY - Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Brookdale University Hospital and Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11212
Country
United States
Facility Name
New York Methodist Hospital - SC/Thalassemia Program
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
Interfaith Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11238
Country
United States
Facility Name
Presbyterian Blume Pediatric Hematology-Oncology Clinic
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
University of Tennessee Cancer Institute
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0306
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30021096
Citation
Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med. 2018 Jul 19;379(3):226-235. doi: 10.1056/NEJMoa1715971.
Results Reference
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A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia
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