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

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ClinicalTrials.gov Identifier: NCT01179217

Recruitment Status : Completed

First Posted : August 11, 2010

Results First Posted : August 10, 2017

Last Update Posted : August 19, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Emmaus Medical, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Anemia Sickle ß0-Thalassemia	Drug: L-glutamine Drug: Placebo	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	230 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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 Start Date :	May 2010
Actual Primary Completion Date :	March 2014
Actual Study Completion Date :	March 2014

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Sickle cell disease

MedlinePlus related topics: Anemia Thalassemia

Drug Information available for: Glutamine

Genetic and Rare Diseases Information Center resources: Thalassemia Sickle Cell Anemia

U.S. FDA Resources

Arms and Interventions

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

Arm

Intervention/treatment

Experimental: L-glutamine

Patients will be randomized to receive investigational product, L-Glutamine.

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

Placebo Comparator: 100% maltodextrin

Patients will be randomized to receive Placebo.

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

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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.

Eligibility Criteria

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Ages Eligible for Study:	5 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01179217

Locations

Show 31 study locations

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United States, Alabama
University of South Alabama Medical Center
Mobile, Alabama, United States, 36617
United States, Arizona
Phoenix Children's Hospital Center for Cancer and Blood Disorders
Phoenix, Arizona, United States, 85016
United States, California
Kaiser Permanente
Inglewood, California, United States, 90301
Children's Hospital & Research Center at Oakland
Oakland, California, United States, 94609
Children's Hospital of Orange County
Orange, California, United States, 92868
Harbor-UCLA Medical Center
Torrance, California, United States, 90509
United States, Colorado
University of Denver School of Medicine Sickle Cell Treatment & Research Center
Aurora, Colorado, United States, 80045
United States, District of Columbia
Howard University Hospital & Howard University
Washington, District of Columbia, United States, 20060
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0296
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta at Egleston/Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Louisville School of Medicine
Louisville, Kentucky, United States, 40202
United States, Louisiana
Sickle Cell Center of S. Louisiana, Tulane University School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, Nevada
Children's Specialty Center of Nevada
Las Vegas, Nevada, United States, 89109
Comprehensive Cancer Center of Nevada
Las Vegas, Nevada, United States, 89109
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
United States, New York
Bronx Lebanon Hospital
Bronx, New York, United States, 11203
The Brooklyn Hospital Center
Brooklyn, New York, United States, 11201
SUNY - Downstate Medical Center
Brooklyn, New York, United States, 11203
Brookdale University Hospital and Medical Center
Brooklyn, New York, United States, 11212
New York Methodist Hospital - SC/Thalassemia Program
Brooklyn, New York, United States, 11215
Interfaith Medical Center
Brooklyn, New York, United States, 11238
United States, North Carolina
Presbyterian Blume Pediatric Hematology-Oncology Clinic
Charlotte, North Carolina, United States, 28204
United States, Tennessee
University of Tennessee Cancer Institute
Memphis, Tennessee, United States, 38104
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0306

Sponsors and Collaborators

Emmaus Medical, Inc.

Investigators

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Study Director:	Yutaka Niihara, MD, MPH	Chairman and CEO

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Emmaus Medical, Inc.
ClinicalTrials.gov Identifier:	NCT01179217
Other Study ID Numbers:	GLUSCC09-01
First Posted:	August 11, 2010 Key Record Dates
Results First Posted:	August 10, 2017
Last Update Posted:	August 19, 2020
Last Verified:	July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Emmaus Medical, Inc.:


Sickle Cell Anemia Sickle Cell Pain Crises Painful Crises Sickle Cell Pain Vaso-occlusive Crises

Additional relevant MeSH terms:

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Anemia Thalassemia Anemia, Sickle Cell Hematologic Diseases	Anemia, Hemolytic, Congenital Anemia, Hemolytic Hemoglobinopathies Genetic Diseases, Inborn

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