Clinical trial NCT01179217: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Anemia
Sickle ß0-Thalassemia
Keywords: Sickle Cell Anemia
Sickle Cell Pain Crises
Painful Crises
Sickle Cell Pain
Vaso-occlusive Crises
Lead sponsor: Emmaus Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2010-08-11
Enrollment: 230
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Number of Occurrences of Sickle Cell Crises
timeFrame: 48 weeks
Secondary outcomes:
measure: The Number of Hospitalizations for Sickle Cell Pain
timeFrame: 48 weeks
measure: The Number of Emergency Room/Medical Facility Visits for Sickle Cell Pain
timeFrame: 48 weeks
measure: The Effect of Oral -L-glutamine on Hematological Parameters
timeFrame: Baseline, Week 4, 24 and 48
measure: The Effect of Oral L-glutamine on Vital Signs
timeFrame: Baseline, Week 4, 24, and 48
measure: The Effect of Oral L-glutamine on Hematological Parameters
timeFrame: Baseline, Week 4, 24 and 48
measure: The Effect of Oral L-glutamine on Hematological Parameters
timeFrame: Baseline, Week 4, 24 and 48
measure: The Effect of Oral L-glutamine on Vital Signs
timeFrame: Baseline, Week 4, Week 24 and Week 48
measure: Effect of Oral L-glutamine on Vital Signs
timeFrame: Baseline, Week 4, Week 24 and Week 48
measure: The Effect of Oral L-glutamine on Vital Signs
timeFrame: Baseline, Week 4, Week 24 and Week 48
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital Center for Cancer and Blood Disorders
state: Arizona
city: Inglewood
country: United States
facility: Kaiser Permanente
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center at Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Denver School of Medicine Sickle Cell Treatment & Research Center
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital & Howard University
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston/Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Louisville
country: United States
facility: University of Louisville School of Medicine
state: Kentucky
city: New Orleans
country: United States
facility: Sickle Cell Center of S. Louisiana, Tulane University School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Las Vegas
country: United States
facility: Children's Specialty Center of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hospital
state: New York
city: Brooklyn
country: United States
facility: The Brooklyn Hospital Center
state: New York
city: Brooklyn
country: United States
facility: SUNY - Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: Brookdale University Hospital and Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital - SC/Thalassemia Program
state: New York
city: Brooklyn
country: United States
facility: Interfaith Medical Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Blume Pediatric Hematology-Oncology Clinic
state: North Carolina
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Chairman and CEO
name: Yutaka Niihara, MD, MPH
role: STUDY_DIRECTOR
References:
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.