Arginine Therapy for the Treatment of Pain in Children With Sickle Cell Disease (R34 pK/PD)

Emory University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Sickle Cell Disease

Treatments: Drug: Arginine (Continuous); Drug: Arginine (Loading); Drug: Arginine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02447874

1K24AT009893-01 (U.S. NIH Grant/Contract)

IRB00077736

Details and patient eligibility

About

The purpose of this study is to determine whether giving extra arginine to patients with sickle cell disease seeking treatment for vaso-occlusive painful events (VOE) will decrease pain scores, decrease need for pain medications or decrease length of hospital stay or emergency department visit.

Full description

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.

Available data suggest that, L-arginine is a safe & efficacious intervention with narcotic-sparing effects in pediatric SCD patients with VOE. The addition of a higher loading dose to the standard dose or use of a continuous infusion may provide additional clinical benefits by overcoming multiple mechanisms that limit global arginine bioavailability in SCD.

Enrollment: 21 estimated patients

Sex: All

Ages: 7 to 21 years old

Volunteers: No Healthy Volunteers

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
• 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
• Use of inhaled nitric oxide, sildenafil or arginine within the last 14 days
• Not an appropriate candidate in the investigator's judgement

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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21 participants in 6 patient groups

Standard dose

Experimental group

Description:

Subjects with sickle cell disease (SCD) and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of a standard dose of arginine (100 mg/kg) three times a day for seven days or until discharged from the hospital, whichever occurs first

Treatment:

Drug: Arginine

Loading dose + standard dose

Experimental group

Description:

Subjects with sickle cell disease and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of an initial loading dose of arginine (200 mg/kg) given over 30 minutes and then receive an intravenous (IV) infusion of a standard dose of arginine (100 mg/kg) three times a day for seven days or until discharged from the hospital, whichever occurs first

Treatment:

Drug: Arginine

Drug: Arginine (Loading)

Loading dose + continuous infusion

Experimental group

Description:

Subjects with sickle cell disease and vaso-occlusive painful events (VOE) will be randomized to receive an intravenous (IV) infusion of an initial loading dose of arginine (200 mg/kg) given over 30 minutes and then receive a continuous intravenous (IV) infusion of 300 mg/kg/24hr for 7 days or until discharged from the hospital, whichever occurs first

Treatment:

Drug: Arginine (Loading)

Drug: Arginine (Continuous)

Non-Randomized Loading dose 500 mg/kg + standard dose

Experimental group

Description:

Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 500 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.

Treatment:

Drug: Arginine (Loading)

Non-Randomized Loading dose 300 mg/kg + standard dose

Experimental group

Description:

Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 300 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.

Treatment:

Drug: Arginine (Loading)

Non-Randomized Loading dose 400mg/kg + standard dose

Experimental group

Description:

Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) arginine dose at 400 mg/kg once, followed by a standard dose of 100mg/kg every 8 hours until discharge or for a total of 21 doses of arginine, whichever comes first.

Treatment:

Drug: Arginine (Loading)