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

Official title

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)

Overview

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

Detailed description

This is a single-center phase 2 randomized double-blind, placebo-controlled trial of intravenous L-citrulline for sickle cell patients ages 4 to 21 years experiencing a vaso-occlusive pain crisis episode (VOE). Eligible subjects will have a documented history of sickle cell disease and inpatient hospitalization for treatment of acute pain with parenteral opioid. Subjects will be randomized to receive high dose intravenous L-citrulline, low dose intravenous L-citrulline or placebo in addition to standard of care. Subjects will be followed closely to evaluate time-to-crisis resolution as the primary outcome defined by time from first dose of intravenous study drug/placebo to the last dose of parenteral opioid prior to hospital discharge. Participants will be monitored for any adverse events including 30-day re-hospitalization rates. Total opioid consumption during the time-to-crisis resolution will be compared between the three arms. In addition, exploratory outcomes will be evaluated for pain score, tissue blood flow, genetic and candidate biomarkers related to vaso-occlusion.

Objectives Primary Objective

• To demonstrate the efficacy of intravenous L-citrulline in reducing the time-to-crisis resolution in sickle cell subjects experiencing a vaso-occlusive pain crisis episode (VOE).

Secondary Objectives

* To evaluate the safety of intravenous L-citrulline in the treatment of VOE * To determine if intravenous L-citrulline improves cumulative opioid consumption during the treatment of VOE Exploratory Objectives * To determine if intravenous L-citrulline improves pain scores during the hospitalization * To determine if intravenous L-citrulline improves 30-day re-hospitalization rates * To determine the pharmacokinetic (PK) profile of intravenous L-citrulline * To evaluate whether intravenous L-citrulline improves tissue blood flow and candidate biomarkers related to vaso-occlusion. * To assess whether genetic single nucleotide polymorphisms related to the nitric oxide pathway influence study outcomes

Interventions

• Drug L-citrulline
  Intravenous L-citrulline (50 mg/kg + 9mg/kg/hr.) for 16 hours
• Other Placebo
  Isotonic normal saline
• Drug L-citrulline
  Intravenous L-citrulline (25 mg/kg + 9mg/kg/hr.) for 16 hours

Primary outcome measures

• Time-to-crisis resolution [Time frame: Baseline to 30 days]

Secondary outcome measures (3)

• Safety [Time frame: Baseline to 30 days]
• Opioid consumption [Time frame: Baseline to 30 days]
• Pain scores [Time frame: Baseline to 30 days]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Children's National Hospital — Washington D.C.

Identifiers

NCT: NCT06635902 · 00000880 · 1R61HL167806

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗