Arginine Therapy for the Treatment of Pain in Children With Sickle Cell Disease

Arginine is a simple amino acid that is found in many foods and is part of the proteins in a
human's body. Patients with sickle cell disease have low levels of the amino acid arginine
and these low levels may be related to pain episodes. Increasing levels of arginine in the
blood may lower pain and/or lower the amount of pain medication (like morphine) that is
needed to treated them. It may also decrease the amount of time spent in the hospital.

Inclusion Criteria:

- Established diagnosis of sickle cell disease--Hemoglobin SS (Hb-SS) or Sβᴼ-thalassemia

- 7-21 years of age

- Weight >= 25kg (55lbs)

- Pain requiring medical care in an acute care setting (emergency department (ED),
hospital ward, day hospital, clinic) requiring parenteral opioids, not attributable to
non-sickle cell causes.

Exclusion Criteria:

- Decision to discharge home from acute care setting.

- Diagnosis of sickle cell disease with any of the following types: hemoglobin SC
disease (HbSC), hemoglobin beta thalassemia (Hb-Beta Thal), hemoglobin SD disease
(HbSD), hemoglobin SE disease (HbSE), hemoglobin SO disease (HbSO), hemoglobin AS
carrier (Hb AS)

- Hemoglobin less than 5 gm/dL

- Immediate Red cell transfusion anticipated

- Hepatic dysfunction: serum glutamic pyruvic transaminase (SGPT) > 3X upper value

- Renal dysfunction: Creatinine >1.0 or 2 x baseline

- Mental status or neurological changes

- Acute stroke or clinical concern for stroke

- Pregnancy

- Allergy to arginine

- Previous hospitalization < 7 days

- Previous randomization in this arginine pK study (patient consented and screened
failed before receiving study drug or placebo remains eligible for future
participation)

- Use of inhaled nitric oxide, sildenafil or arginine within the last month