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

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