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

Официальное название

Arginine Therapy for the Treatment of Vaso-Occlusive Events in Children With Severe Sickle Cell Disease

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Arginine
  Arginine will be dispensed intravenously (in the vein) in the standard dose of arginine as 100 mg/kg three times a day for seven days or until discharge. * Loading dose: 200 mg/kg once * Continuous IV: 300 mg/kg/24 hours
• Препарат Arginine (Loading)
  Arginine will be dispensed intravenously (in the vein) as an initial bolus (loading) at each specified group dose 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.
• Препарат Arginine (Continuous)
  Arginine will be dispensed intravenously (in the vein) as a continuous IV infusion of 300 mg/kg/24hr

Первичные конечные точки

• Pharmacokinetics of IV arginine, measured by plasma arginine concentration over time [Срок оценки: Day 1 through study completion, an average of up to 7 days]
• Change in nitric oxide metabolites [Срок оценки: Baseline, day 1 through study completion, an average of up to 7 days]

Вторичные конечные точки (12)

• Area Under the Plasma Concentration -Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration for Arginine [Срок оценки: Day 1]
• Maximum observed plasma concentration of arginine [Срок оценки: Day 1]
• Apparent clearance of arginine [Срок оценки: Day 1]
• Terminal elimination half-life (t1/2) for arginine [Срок оценки: Day 1]
• Change in red blood cell (RBC) arginine [Срок оценки: Baseline, day 1 through study completion, an average of up to 7 days]
• Daily urine arginine [Срок оценки: From Day 1 until study completion, an average of up to 7 days]
• Global arginine bioavailability (GABR) [Срок оценки: From enrollment through study completion, an average of up to 7 days]
• Change in asymmetric dimethylarginine (ADMA) levels [Срок оценки: Baseline, day 1 and through study completion, an average of up to 7 days]
• Modeling nitric oxide (NOx) level versus plasma arginine level [Срок оценки: From enrollment through study completion, an average of up to 7 days]
• Biomarkers of hemolysis [Срок оценки: From enrollment through study completion, an average of up to 7 days]
• Erythrocyte glutathione levels [Срок оценки: From enrollment through study completion, an average of up to 7 days]
• Level of cytokines [Срок оценки: From enrollment through study completion, an average of up to 7 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Children's Healthcare fo Atlanta at Hughes Spalding — Atlanta
• Children's Healthcare of Atlanta at Arthur M. Blank Hospital — Atlanta

Публикации

• 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. PMID 32384147
• Korman R, Hatabah D, Brown LA, Harris F, Wilkinson H, Rees CA, Bakshi N, Archer DR, Dampier C, Morris CR. Impact of arginine therapy on kyotorphin in children with sickle cell disease and vaso-occlusive pain. Blood Adv. 2024 Jun 25;8(12):3267-3271. doi: 10.1182/bloodadvances.2023012209. PMID 38527291
• Korman R, Yasmine M, Hatabah D, Alzraikat N, Harris F, Brown LA, Chonat S, Bakshi N, Rees CA, Dampier C, Morris CR. Secretory Phospholipase A2 in Patients With Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain Episodes. Pediatr Blood Cancer. 2026 Aug 4:e70615. doi: 10.1002/1545-5017.70615. Online ahead of print. PMID 42549972

Идентификаторы

NCT: NCT02447874 · IRB00077736 · 1K24AT009893-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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