Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
- Registration Number
- NCT00513617
- Lead Sponsor
- UCSF Benioff Children's Hospital Oakland
- Brief Summary
Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited genetic disease that can cause intense pain episodes. This study will evaluate the effectiveness of the nutritional supplement arginine at improving blood cell function and disease symptoms in people with SCD.
- Detailed Description
SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain that are called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen. In people with SCD, the abnormal hemoglobin distorts the shape of the red blood cells. This causes the red blood cells to clump together, decreasing blood flow and oxygen delivery to the body's tissues. The reduced levels of oxygen can lead to sickle cell crises and tissue damage. Hemolysis, the destruction of red blood cells, is also a hallmark of SCD. During hemolysis, hemoglobin is released into the bloodstream, where it removes nitric oxide (NO), a natural chemical in the body that expands blood vessels. Arginase, another protein released during hemolysis, removes arginine from the bloodstream, which can also lead to decreased NO levels. The lack of NO constricts blood vessels, further contributing to painful sickle cell crises. Arginine supplementation may increase healthy hemoglobin and NO production and, in turn, prevent or reduce sickle cell crises. The purpose of this study is to evaluate the effectiveness of arginine at increasing NO levels, improving red blood cell function, and reducing hospitalizations and pain medication use in people with SCD.
This study will enroll children and adults with SCD. Participants will be randomly assigned to receive twice daily doses of either a low dose of arginine, a high dose of arginine, or placebo for 12 weeks. Study visits will occur at baseline, three times during Month 1, and Weeks 8, 12, 14, and 16. Each study visit will include an echocardiogram to measure heart activity, blood collection, and a medical history review to identify adverse events, pain medication usage, headaches, emergency department visits, and hospitalizations.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 128
- Established diagnosis of H SS or S-beta thalassemia
- History of at least one vaso-occlusive pain event in the 12 months prior to study entry
- Regular compliance with comprehensive medical care
- In a steady disease state and not in the midst of any acute complication due to SCD at study entry
- Inability to take or tolerate oral medications
- Liver dysfunction (i.e., SGPT level greater than or equal to two times the normal limit and albumin level less than or equal to 3.2 g/dL)
- Kidney dysfunction ( i.e., creatinine level greater than or equal to 1.2 mg/dL for children and greater than or equal to 1.4 mg/dL for adults)
- Allergy to arginine
- Pregnant
- Received a blood transfusion within the 90 days prior to study entry
- More than 10 hospital admissions for pain in the 12 months prior to study entry
- Daily use of opioids and experiencing unstable pain that interferes with work or daily routine
- Required more than 3 hospital admissions and more than 10 emergency department/day hospital visits in the 12 months prior to study entry
- Received treatment with hydroxyurea within the 90 days prior to study entry
- Received treatment with any investigational drug in the 90 days prior to study entry
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo No Arginine Low Dose Arginine 0.05 g/kg/day Arginine High Dose Arginine 0.10 g/kg/day Arginine
- Primary Outcome Measures
Name Time Method Mean Corpuscular Hemoglobin Concentration 12 weeks after randomization Mean corpuscular hemoglobin concentration as measured by an Advia machine
Gardos Channel Activity 12 weeks after randomization Gardos channel activity: a calcium (Ca2+)-activated K+ channel
Nitric Oxide 12 weeks after randomization Nitric oxide from plasma amino acids
- Secondary Outcome Measures
Name Time Method Soluble Vascular Cell Adhesion Molecule 12 weeks after randomization Soluble vascular cell adhesion molecule (sVCAM) a vascular adhesion molecule
8-iso-PGF2a 12 weeks after randomization 8-iso-PGF2a is a measure of lipid peroxidation and oxidative damage in vivo measured by enzyme immunoassay kit from Cayman chemical
Endothelin-1 12 weeks after randomization Endothelin-1 is a potent vasoconstrictor and pro-inflammatory agent which is elevated in SCD patients
Fetal Hemoglobin 12 weeks after randomization Fetal hemoglobin (HbF) as measured by the Advia machine
Trial Locations
- Locations (17)
University of Mississippi Medical Center (Pediatric)
🇺🇸Jackson, Mississippi, United States
Children's Medical Center of Dallas
🇺🇸Dallas, Texas, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Oakland and Research Institute
🇺🇸Oakland, California, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
University of California - San Francisco
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Colorado at Denver and Health Sciences Center--Sickle Cell Treatment and Research Center
🇺🇸Denver, Colorado, United States
Children's Hospital of Montefiore
🇺🇸Bronx, New York, United States
St. Christopher's Children's Research Hospital
🇺🇸Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Mississippi Medical Center (Adult)
🇺🇸Jackson, Mississippi, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States