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

Sickle Cell Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01179217
• Other study ID #: GLUSCC09-01
• Status: Completed
• Phase: Phase 3
• Start date: May 2010
• Est. completion date: March 2014

Study information

• Verified date: July 2017
• Source: Emmaus Medical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell
• Sickle Cell Anemia
• Sickle ß0-Thalassemia
• Thalassemia

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Emmaus Medical, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 weeks
Secondary	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.	48 weeks
Secondary	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.	48 weeks
Secondary	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.	Baseline, Week 4, 24 and 48
Secondary	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.	Baseline, Week 4, 24, and 48
Secondary	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.	Baseline, Week 4, 24 and 48
Secondary	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.	Baseline, Week 4, 24 and 48
Secondary	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.	Baseline, Week 4, Week 24 and Week 48
Secondary	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.	Baseline, Week 4, Week 24 and Week 48
Secondary	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.	Baseline, Week 4, Week 24 and Week 48