Intravenous L-Citrulline for Vaso-occlusive Pain Episode in Sickle Cell Disease

NCT06635902 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 000008801R61HL167806
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if intravenous citrulline works to treat acute pain in hospitalized patients with sickle cell disease. It will also learn about the safety of intravenous citrulline. The main questions it aims to answer are:

• Does intravenous citrulline decrease the duration of sickle cell pain during hospitalization
• What medical problems do participants have when taking intravenous citrulline? Researchers will compare intravenous citrulline to a placebo (a look-alike substance that contains no drug) to see if intravenous citrulline works to treat acute pain. Participants will:
• Receive baseline tests and intravenous citrulline for 16 hours during the hospital stay
• After hospital discharge, visit the clinic in about 30 days for checkup and tests

Conditions

Sickle Cell Disease; Vaso-occlusive Pain Episode

Keywords

sickle cell disease; sickle cell pain crisis; citrulline

Outcome Measures

Primary Outcomes (1)

• Time-to-crisis resolution

  Change in time-to-crisis resolution as defined by the time (in hours) from first dose of intravenous study drug or placebo to the time of last dose of intravenous opioid during hospitalization

  Baseline to 30 days

Secondary Outcomes (3)

• Safety

  Baseline to 30 days

• Opioid consumption

  Baseline to 30 days

• Pain scores

  Baseline to 30 days

Other Outcomes (5)

• Citrulline and arginine bioavailability

  Baseline to 30 days

• Nitric oxide

  Baseline to 30 days

• Cytokine interleukin IL-1ß

  Baseline to 30 days

Study Arms (3)

Low dose intravenous L-citrulline

EXPERIMENTAL

Drug: L-citrulline

High dose intravenous L-citrulline

EXPERIMENTAL

Drug: L-citrulline

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

L-citrulline DRUG

Intravenous L-citrulline (50 mg/kg + 9mg/kg/hr.) for 16 hours

High dose intravenous L-citrulline

Placebo OTHER

Isotonic normal saline

Placebo

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Suvankar Majumdar: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Citrulline

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

Study Officials

• Suvankar Majumdar, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jillian Baker, RN

CONTACT

202-476-1311; jbaker5@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of Hematology

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 10, 2024
• Study Start: December 22, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Beginning 3 months and ending 3 years after the publication of results
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP). For more information or to submit a request, please contact smajumdar@childrensnational.org

Locations

US (1)