Using intravenous L-citrulline to treat pain in sickle cell disease

A Phase 2 Randomized Double-blind, Placebo-controlled Clinical Trial of Intravenous Citrulline for Vaso-occlusive Pain Episode in Hospitalized Patients With Sickle Cell Disease (CONQUER SCD Pain Trial)

This study is testing if giving L-citrulline through an IV can help kids and young adults with sickle cell disease feel better faster during painful episodes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 99 (estimated)
• Ages: 4 Years to 21 Years
• Sex: All
• Sponsor: Children's National Research Institute (Academic / other)
• Locations: 1 site (Washington D.C., District of Columbia)
• Trial ID: NCT06635902 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and safety of intravenous L-citrulline in treating acute vaso-occlusive pain episodes in hospitalized patients with sickle cell disease. Participants aged 4 to 21 years will be randomized to receive either high-dose L-citrulline, low-dose L-citrulline, or a placebo alongside standard care. The primary outcome is the time-to-crisis resolution, measured from the first dose of the study drug to the last dose of parenteral opioids before discharge. Participants will also be monitored for adverse events and will return for follow-up 30 days post-discharge.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 4 to 21 years with a documented history of sickle cell disease and currently hospitalized for a vaso-occlusive pain episode.

Not a fit: Patients with chronic pain conditions, severe anemia, or other complications related to sickle cell disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce pain duration and opioid consumption for patients experiencing vaso-occlusive crises.

How similar studies have performed: While the use of L-citrulline in this context is novel, similar studies exploring alternative treatments for vaso-occlusive crises have shown promise.

Eligibility criteria

Inclusion Criteria:

* Sickle cell disease (all genotypes)
* Patients with sickle cell disease ages 4 to 21 years old
* Presence of sickle cell vaso-occlusive pain episode requiring hospitalization and parenteral opioid therapy
* Able to randomize to study drug/placebo within 12 hours of first dose of parenteral opioid in the Emergency Department

Exclusion Criteria:

* Current pain lasting \>3 days.
* \>9 hospitalizations in the prior year
* Presence of any other complication related to sickle cell disease requiring the hospitalization such as splenic sequestration, hepatic sequestration, stroke, transient ischemic attack, etc.
* History of opioid use disorder, chronic pain or medical regimen requiring daily opioid use.
* Severe anemia (hemoglobin \<6g/dL)
* Pregnant (as confirmed by a positive urine pregnancy test) or lactating female.
* Alanine/aspartate transferase \>2x upper limit of normal laboratory range for age.
* Subject has the following serum creatinine:

  * Age 4 to 13 years \> 0.9 mg/dL
  * Age 14 to 17 years 1.0 mg/dL
  * Age ≥18 years \>1.5mg/dL
* Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability
* Use of L-glutamine
* History of allergic reaction to L-citrulline products

Where this trial is running

Washington D.C., District of Columbia

• Children's National Hospital — Washington D.C., District of Columbia, United States (Recruiting)

Study contacts

• Principal investigator: Suvankar Majumdar, MD — Children's National Research Institute
• Study coordinator: Jillian Baker, RN

Conditions Sickle Cell Disease; Vaso-occlusive Pain Episode; sickle cell disease; sickle cell pain crisis; citrulline