Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 2 Randomized Control Trial of Arginine Therapy for Pediatric Sickle Cell Disease Pain
Brief Summary: The aim of this study is to determine whether giving extra arginine, a simple amino acid, to patients with sickle cell disease seeking treatment for a pain crisis (vaso-occlusive painful events (VOE) will decrease pain scores, decrease the need for pain medications or decrease length of hospital stay or emergency department visit. Funding Source - FDA OOPD.


Options:
A: 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
B: Inclusion Criteria:

* Established diagnosis of sickle cell disease (SCD); all genotypes
* Pain requiring medical care in an acute care setting (such as the emergency department or ED, hospital ward, day hospital, clinic) not attributable to non-sickle cell causes, that is moderate-to-severe requiring parenteral opioids

Exclusion Criteria:

* Decision to discharge home from the acute care setting
* Hemoglobin less than 5 gm/dL or immediate need for red cell transfusion anticipated within next 12 hours
* Hepatic dysfunction of SGPT greater than 3 times the upper value
* Renal dysfunction of creatinine greater than 1.0
* Mental status or neurological changes
* Acute stroke or clinical concern for stroke
* Pregnancy
* Allergy to arginine
* Two (2) or more ED visits for VOE within the last 7 days prior to CURRENT ED visit
* Hospitalization within 14 days
* Previous randomization in this arginine RCT (patient consented and screen failed before receiving study drug or placebo remains eligible for future participation).
* Use of inhaled nitric oxide, sildenafil or arginine within the last month
* PICU admission from the emergency department
* Hypotension requiring treatment with clinical intervention
* Acidosis with Co2≤ 16
* Newly started on HU for \<3 months
* Not an appropriate candidate in the investigator's judgment
* Patient refusal
C: Inclusion Criteria:

Subjects who meet all of the following criteria are eligible for enrollment into the study:

* Participant has signed the informed consent/assent with parent signing informed consent as age appropriate.
* Established diagnosis of HbSS or HbSβo Thal.
* History of ≥3 vasocclusive pain events in preceding 12 months.
* Regular compliance with comprehensive care.
* Aged 10 years or greater and less than 20 years.
* At enrollment, subject should be in his/her steady or baseline state.

Exclusion Criteria

* Subjects with Hb levels \<5.5gm/dL.
* Inability to take or tolerate oral medications.
* Poor compliance with previous treatment regimens.
* Hepatic dysfunction (SGPT also known as ALT \>2X upper limit of normal or conjugated bilirubin \>2X the patients baseline within the last 6 weeks).
* Renal dysfunction (A creatinine level within the past 6 weeks of ≥ 1.0mg/dL for children and ≥ 1.2mg/dL for a subject ≥ 18 years of age).
* Allergy to fish or shell fish.
* Triglyceride levels \<80mg/dL.
* Pregnancy.
* Chronic Transfusion Therapy.
* Transfusion within the last 30 days.
* Persistent pain from sickle-complications (e.g. avascular necrosis).
* A vasocclusive pain episode lasting longer than 2 weeks or \>12 pain episodes in preceding year.
* Daily narcotic usage.
* Treatment with any investigational drug or regular fish oil supplementations in last 60 days.
* Currently receiving another investigational agent, or on such an agent with the last 60 days.
* Dosage changes in preceding 3 months if on hydroxyurea.
* Bleeding disorder or patient on concomitant anti-coagulation.
* Conditional or abnormal TCD result or stroke.
* Other chronic illness that could adversely affect subjects performance such as HIV or TB.
* Children in Care (CiC): A child in care is a child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
D: 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.

Answer: B