UCSF Benioff Children’s Hospital Oakland clinical researchers, in conjunction with other sickle cell centers and scientists at Emmaus Life Sciences Inc., have demonstrated that therapy with L-Glutamine reduced the frequency of pain episodes in both pediatric and adult patients with sickle cell disease (SCD). The results of the 48-week, phase 3 clinical trial are published in the July 19, 2018, issue of New England Journal of Medicine.
The paper, “A Phase 3 Trial of L-Glutamine in Sickle Cell Disease,” documented the effects of taking Endari, a prescription-grade, pharmaceutical form of L-glutamine, as compared to placebo, for 230 patients aged 5 to 58 years of age with sickle cell disease. Endari was approved in July 2017 by the U.S. Food and Drug Administration based on the safety and efficacy data from this study. Glutamine is an amino acid that is involved in several biochemical reactions.
The study showed that whether administered alone or with hydroxyurea, L-glutamine reduced the frequency of sickle cell pain crises by 25 percent (a median of three events per patient in the L-glutamine group and four in the placebo group) and hospitalizations by 33 percent (a median of two hospitalizations in the L-glutamine group and three in the placebo group). Additional findings showed lower cumulative hospital days of 41 percent and a lower incidence of dangerous acute chest syndrome (ACS) by more than 60 percent.
“This study validated research on the safety of pharmaceutical grade L-glutamine which has antioxidant properties that improves the NAD redox potential in sickle cell patients. Safe neutraceuticals are of major importance to the sickle cell community,” said Elliott Vichinsky, MD, director of Hematology/Oncology at the Northern California Sickle Center at UCSF Benioff Children’s Hospital Oakland. “Our clinical trial found that L-glutamine, which does not require any routine laboratory monitoring, decreases pain events in patients by itself or in combination with hydroxyurea. It is a major advance in therapy for sickle cell disease and offers families safe, new therapeutic options.”
Sickle cell disease is a genetic blood disorder that causes a distortion in the shape of red blood cells. This leads to the many symptoms and medical problems affecting children and adults with sickle cell disease, including pain, anemia, and bone, kidney, lung and neurologic problems.
“Endari, is the first approved treatment for sickle cell disease in pediatric patients 5 years of age and older and the first in nearly 20 years for adults,” said study co-author Yutaka Niihara, MD, CEO and founder of Emmaus, which produces the product. “Our hope in sharing the results of this data from the New England Journal of Medicine is to increase awareness of sickle cell disease, a lifelong hereditary blood disorder which commonly affects those of African descent, as well those from Central and South America and people of Middle Eastern, Asian, Indian and Mediterranean descent. It is important for patients to know that they have a treatment option for this debilitating disease.”
The double-blind trial evaluated the efficacy and safety of pharmaceutical-grade L-glutamine administered twice daily by mouth, as compared with placebo, in reducing the frequency of pain crises among patients with sickle cell anemia or sickle β0-thalassemia and a history of two or more pain crises during the previous year. Patients who were receiving hydroxyurea at a dose that had been stable for at least 3 months before screening continued that therapy through the 48-week treatment period.
Patients were randomly assigned, in a 2:1 ratio, to receive L-glutamine (152 patients) or placebo (78 patients). Those in the L-glutamine group had significantly fewer pain crises than those in the placebo group (P = 0.005) and fewer hospitalizations (P = 0.005). Approximately 54 percent of the patients were female and 66 percent of the patients in both trial groups were already receiving hydroxyurea. The study found that low-grade nausea, non-cardiac chest pain, fatigue and musculoskeletal pain occurred more frequently in the L-glutamine group than in the placebo group.
Funding for this trial was provided by Emmaus Life Sciences Inc.
Study authors for the Phase 3 Trial of l-Glutamine in Sickle Cell Disease include Yutaka Niihara, M.D., M.P.H., Emmaus Medical, Torrance and University of California at Los Angeles; Scott T. Miller, M.D., State University of New York-Downstate Medical Center; Julie Kanter, M.D., Medical University of South Carolina, Charleston; Sophie Lanzkron, M.D., M.H.S., Johns Hopkins Hospital, Baltimore; Wally R. Smith, M.D., Virginia Commonwealth University Healthcare Systems, Richmond; Lewis L. Hsu, M.D., Ph.D., Victor R. Gordeuk, M.D., University of Illinois at Chicago, Chicago; Kusum Viswanathan, M.D., Brookdale University Hospital and Medical Center; Sharada Sarnaik, M.D., Children’s Hospital of Michigan, Detroit; Ifeyinwa Osunkwo, M.D., Carolinas HealthCare System, Charlotte, NC; Edouard Guillaume, M.D., Interfaith Medical Center; Swayam Sadanandan, M.D., Brooklyn Hospital Center; Lance Sieger, M.D., Osbourne A. Blake, M.D., Los Angeles, Kaiser Permanente Medical Center, Inglewood; Joseph L. Lasky, M.D., Eduard H. Panosyan, M.D., Harbor–UCLA and Los Angeles BioMedical Research Institute; Tamara N. New, M.D., Children’s Healthcare of Atlanta, Emory University, Atlanta; Rita Bellevue, M.D., New York Presbyterian Brooklyn Methodist Hospital; Lan T. Tran, M.P.H., Rafael L. Razon, M.D., Charles W. Stark, Pharm.D., Emmaus Medical, Torrance; Lynne D. Neumayr, M.D., and Elliott P. Vichinsky, M.D., UCSF Benioff Children’s Hospital Oakland Research Center, Oakland.
UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals – UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland – as well as Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. UCSF faculty also provide all physician care at the public Zuckerberg San Francisco General Hospital and Trauma Center, and the SF VA Medical Center. The UCSF Fresno Medical Education Program is a major branch of the University of California, San Francisco’s School of Medicine.