Clinical trial NCT02447874: Arginine Therapy for the Treatment of Pain in Children With Sickle Cell Disease
Official title: Arginine Therapy for the Treatment of Vaso-Occlusive Events in Children With Severe Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Children's Healthcare of Atlanta
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2015-05-19
Enrollment: 21
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics of IV arginine, measured by plasma arginine concentration over time
timeFrame: Day 1 through study completion, an average of up to 7 days
measure: Change in nitric oxide metabolites
timeFrame: Baseline, day 1 through study completion, an average of up to 7 days
Secondary outcomes:
measure: Area Under the Plasma Concentration -Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration for Arginine
timeFrame: Day 1
measure: Maximum observed plasma concentration of arginine
timeFrame: Day 1
measure: Apparent clearance of arginine
timeFrame: Day 1
measure: Terminal elimination half-life (t1/2) for arginine
timeFrame: Day 1
measure: Change in red blood cell (RBC) arginine
timeFrame: Baseline, day 1 through study completion, an average of up to 7 days
measure: Daily urine arginine
timeFrame: From Day 1 until study completion, an average of up to 7 days
measure: Global arginine bioavailability (GABR)
timeFrame: From enrollment through study completion, an average of up to 7 days
measure: Change in asymmetric dimethylarginine (ADMA) levels
timeFrame: Baseline, day 1 and through study completion, an average of up to 7 days
measure: Modeling nitric oxide (NOx) level versus plasma arginine level
timeFrame: From enrollment through study completion, an average of up to 7 days
measure: Biomarkers of hemolysis
timeFrame: From enrollment through study completion, an average of up to 7 days
measure: Erythrocyte glutathione levels
timeFrame: From enrollment through study completion, an average of up to 7 days
measure: Level of cytokines
timeFrame: From enrollment through study completion, an average of up to 7 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare fo Atlanta at Hughes Spalding
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
Study officials:
affiliation: Emory University
name: Claudia Morris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morris CR, Brown LAS, Reynolds M, Dampier CD, Lane PA, Watt A, Kumari P, Harris F, Manoranjithan S, Mendis RD, Figueroa J, Shiva S. Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain. Blood. 2020 Sep 17;136(12):1402-1406. doi: 10.1182/blood.2019003672.