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

Conditions

• Sickle Cell Disease

Eligibility Criteria

Sex

ALL

Age

6 Years - 21 Years

Healthy Volunteers

Not accepted

Interventions

• L-citrulline — DRUG
  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.
• Placebo — OTHER
  Placebo intravenous (IV) treatment designed to match the appearance and administration schedule of L-citrulline

Study Details

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.

Key Dates

Start date

Jul 25, 2025

Status verified

May 2025

Primary completion

Jun 30, 2027

Completion

Jun 30, 2029

Study Design

Enrollment

120 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Placebo Comparator: Placebo
  Participants randomized to this arm will receive a placebo intravenous (IV) treatment designed to match the appearance and administration schedule of L-citrulline. The placebo will be given as a single bolus dose followed by a continuous infusion for up to 12 hours. All participants will continue to receive standard of care pain management for sickle cell disease, consistent with the treating site's protocol and adjusted as needed based on the patient's clinical condition.
• Experimental: L-citrulline Intravenous Treatment Arm
  Participants randomized to this arm will receive intravenous (IV) L-citrulline, a naturally occurring amino acid being investigated for its potential to treat vaso-occlusive crises (VOCs) in sickle cell disease. The study drug will be administered as a 50 mg/kg IV bolus, followed by a continuous infusion at 9 mg/kg/hour for up to 12 hours. The investigational product is provided as an isotonic solution in vials containing L-citrulline 50 mg/mL. Treatment will begin within 120 minutes of informed consent/assent and following the initial dose of opioid or ketamine, but prior to any subsequent doses. All participants will continue to receive standard-of-care (SoC) pain management per site protocol, which may be adjusted based on clinical response to study treatment.

Primary Outcome Measure

Change in pain score from baseline to discharge [ Time Frame: From enrollment to hospital discharge (typically within 12 to 72 hours), up to max of 30 day study duration ]

Central Contacts

• Gurdyal Kalsi, MD, MFPM (Hon)
  +1 410-736-3750
  [email protected]
• Heather Hill, BS
  +1 443-691-2474
  [email protected]

Locations (6)

Find similar trials in Washington D.C., DC

Related Studies

• Blood Collection for Research Related to Certain Diseases Involving Blood Vessels
  Enrolling By Invitation · National Heart, Lung, and Blood Institute (NHLBI) · Bethesda, Maryland
• Blood Sampling for Research Related to Sickle Cell Disease
  Recruiting · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Bethesda, Maryland
• Study of Panobinostat (LBH589) in Patients With Sickle Cell Disease
  PHASE1 · Recruiting · Abdullah Kutlar · Augusta, Georgia
• Sickle Cell Clinical Research and Intervention Program
  Recruiting · St. Jude Children's Research Hospital · Peoria, Illinois