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

NCT02447874 | Recruiting Phase 1

• 2 other identifiers: IRB000777361K24AT009893-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics of IV arginine, measured by plasma arginine concentration over time

  Total time plasma arginine levels are maintained above the half-saturating concentration (Km) of cationic amino acid transporter protein-1 (CAT-1), which is 150 µM (normal range of extracellular plasma arginine concentration). pK samples will be collected at 6 time-points within 8 hours: prior to arginine treatment (time 0), and at 60, 90, 120 minutes, 4 and 8 hours after the initiation of arginine therapy, and then every 24 hours up to 7 days.

  Day 1 through study completion, an average of up to 7 days

• Change in nitric oxide metabolites

  The formation of NO metabolites will be measured by determination of its stable end products in serum; nitrite (NO2-) and nitrate (NO3-). Change in nitric oxide metabolites will be calculated as the difference in metabolites from the time prior to arginine treatment (baseline) to the end of the intervention period.

  Baseline, day 1 through study completion, an average of up to 7 days

Secondary Outcomes (12)

• Area Under the Plasma Concentration -Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration for Arginine

  Day 1

• Maximum observed plasma concentration of arginine

  Day 1

• Apparent clearance of arginine

  Day 1

• Terminal elimination half-life (t1/2) for arginine

  Day 1

• Change in red blood cell (RBC) arginine

  Baseline, day 1 through study completion, an average of up to 7 days

Study Arms (6)

Standard dose

EXPERIMENTAL

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

Drug: Arginine

Loading dose + standard dose

EXPERIMENTAL

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

Drug: Arginine; Drug: Arginine (Loading)

Loading dose + continuous infusion

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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.

Drug: Arginine (Loading)

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

EXPERIMENTAL

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.

Drug: Arginine (Loading)

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

EXPERIMENTAL

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.

Drug: Arginine (Loading)

Interventions

Arginine DRUG

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

Also known as: Arginine Hydrochloride Injection, R-Gene® 10

Loading dose + standard dose; Standard dose

Arginine (Loading) DRUG

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.

Also known as: Arginine Hydrochloride Injection, R-Gene® 10

Loading dose + continuous infusion; Loading dose + standard dose; Non-Randomized Loading dose 300 mg/kg + standard dose; Non-Randomized Loading dose 400mg/kg + standard dose; Non-Randomized Loading dose 500 mg/kg + standard dose

Arginine (Continuous) DRUG

Arginine will be dispensed intravenously (in the vein) as a continuous IV infusion of 300 mg/kg/24hr

Also known as: Arginine Hydrochloride Injection, R-Gene® 10

Loading dose + continuous infusion

Eligibility Criteria

• Age: 7 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Children's Healthcare of Atlanta: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (2)

Children's Healthcare fo Atlanta at Hughes Spalding

Atlanta, Georgia, 30303, United States

RECRUITING

Children's Healthcare of Atlanta at Arthur M. Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Related Publications (2)

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Arginine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Claudia Morris, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Reshika Mendis, MBBS

CONTACT

404-785-4525; Reshika.mendis@choa.org

Claudia Morris, MD

CONTACT

404 727-5500; claudia.r.morris@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 19, 2015
• Study Start: May 1, 2015
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

US (2)