Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
Effectiveness of Arginine as a Treatment for Sickle Cell Anemia
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.
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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