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NOT YET RECRUITING

NCT06989567

PHASE3

A Study of Intravenous L-Citrulline in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting to Emergency Departments in Acute Vaso-Occlusive Crisis

Sponsor: Asklepion Pharmaceuticals, LLC

View on ClinicalTrials.gov

Summary

This study is being done to learn more about a possible new treatment for pain episodes (called vaso-occlusive crises or VOCs) in children, teens, and young adults with sickle cell disease (SCD). The study will include about 120 participants between the ages of 6 and 21 who come to the emergency department (ED) with a VOC. A VOC is a painful episode that happens with no clear cause and no signs of infection or major problems with organs like the liver or kidneys. Before joining the study, patients and their families may be asked to learn about it and give permission (called consent or assent) while at a regular clinic visit. If that hasn't happened yet, the consent/assent process will happen at the emergency department when the patient comes in for care. If the patient meets all the study requirements, they can join the treatment part of the study. Participants will be randomly assigned (like flipping a coin) to receive either: L-citrulline, the study drug, or A placebo, which looks the same but has no active ingredients. Everyone has an equal chance of getting either one. The study drug is given through an IV. It starts with one larger dose, followed by a steady infusion for up to 12 hours. All patients in the study will still receive the usual pain treatment (called standard of care), which may include opioids. However, some patients may need fewer opioids if the study treatment helps with their pain. If any medicines are not allowed during the study, the doctor will explain this during the consent process. Patients can go home once: Their pain is controlled with oral (by mouth) pain medicine, They're eating and drinking well, and They've been given a personal pain management plan to use at home. After leaving the hospital, the study team will follow up with patients by phone about 2 days later (within a 12-hour window), again around Day 7, and again around Day 30 to check how they're doing.

Official title: A Phase III, Multi-Center, Double-Blind, Placebo-Controlled, Randomized Study of Intravenous L-Citrulline in Sickle Cell Disease Presenting to Emergency Departments in Acute Vaso-Occlusive Crisis in Children, Adolescents and Young Adults (6 to 21 Years)

Key Details

Gender

All

Age Range

6 Years - 21 Years

Study Type

INTERVENTIONAL

Enrollment

120

Start Date

2025-07-25

Completion Date

2029-06

Last Updated

2025-05-29

Healthy Volunteers

Conditions

Sickle Cell Disease

Interventions

DRUG

L-citrulline

This intervention uses intravenous L-citrulline as an acute treatment for vaso-occlusive crisis (VOC) in sickle cell disease, administered as a 50 mg/kg IV bolus followed by a 9 mg/kg/hr continuous infusion. Unlike other studies that evaluate oral citrulline or chronic VOC prevention, this study focuses on real-time symptom resolution in the emergency department setting by targeting impaired nitric oxide production and vasoconstriction. The selected dosing regimen was optimized in prior studies to achieve a therapeutic plasma concentration associated with improved pain scores and reduced opioid use, distinguishing it mechanistically and clinically from other interventions.

OTHER

Placebo

Placebo intravenous (IV) treatment designed to match the appearance and administration schedule of L-citrulline

Inclusion Criteria: * SCD (all genotypes) * Children, adolescents and young adults between ages 6 to 21 years * In a steady disease state and not in the midst of any acute complication other than VOC due to SCD at study entry * Baseline NRS score \>5 or Faces Pain Scale score ≥6 * For females of childbearing potential, a negative urine pregnancy test and using an adequate method of contraception including abstinence * Patients or parents or legal guardian of the patient who are willing and able to sign and provide consent and assent (where appropriate for the age of the child) * Patients willing to begin study treatment within 120 minutes after providing informed consent/assent and soon after the first/initial dose, but before any subsequent doses of IV opioid or ketamine Exclusion Criteria: * Current pain lasting \>3 days * History of 9 hospital admissions in the prior year * Participation in a clinical trial of a new therapy for SCD within the last 1 month * Presence of any other complication related to SCD such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, acute renal dysfunction, acute chest syndrome and other major medical conditions or organ dysfunction * Hypotension requiring clinical intervention; hemodynamic instability; septic shock * Severe anemia (hemoglobin \<6 g/dL) * Systemic steroid therapy within the last 24 hours * Use of inhaled NO or medications that are known to cause hypotension (e.g., nitrates, sildenafil, tadalafil, vardenafil, osildenafil, or arginine) within the last 30 days * Serum creatinine levels: * Age 6-13 years: \>0.9 mg/dL * Age 14-17 years: \>1.0 mg/dL * Age ≥18 years: \>1.5 mg/dL * Report of fever (\>38°C) within the last 24 hours * Presence of acute chest syndrome, sepsis, known bacterial infection, or hemodynamic instability * Acute mental status or neurological changes * Acute stroke or clinical concern for stroke * Patients with inability to have assent given (ages 6 to 17 years) or consent (ages 18 through 21 years). Note: Parents or legal guardians can provide consent for patients who are unable to provide assent (e.g., sleepy or preoccupied by their pain). * History of allergic reaction to L-citrulline product or dextrose * Unreliable venous access * The PI considers that the patient will be unable to comply with the study requirements * Patients pre-planned for admission on arrival in ED

Locations (6)

Children's National Hospital

Washington D.C., District of Columbia, United States

University of Miami

Coral Gables, Florida, United States

Emory University

Atlanta, Georgia, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

East Carolina (University of North Carolina)

Greenville, North Carolina, United States