A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome

Sickle cell disease is a genetic red blood cell disorder characterized by vaso-occlusion from sickling of red blood cells, that can lead to pain or organ complications such as acute chest syndrome. Sickle cell disease is associated with low amounts of nitric oxide, a compound important for dilating the blood vessel wall. Citrulline is a substance that is known to increase nitric oxide. The goal of this Phase I study are to find the highest safe dose of continuous IV citrulline that can be given to individuals with sickle cell disease experiencing a sickle cell pain crisis or acute chest syndrome without causing severe side effects.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

6 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Sickle cell disease genotypes (HbSS, HbS/β0-thalassemia, HbS/β+-thalassemia, HbSC)
Ages 6 to 50 years old
Patients with sickle cell disease aged 6 to 50 years old Presence of sickle cell pain crisis defined by the presence of pain requiring hospitalization and parental opioid therapy
Presence of acute chest syndrome defined by the presence of a new CXR infiltrate and any one of the following respiratory symptoms of fever, shortness of breath, wheezing, chest pain, cough or new onset hypoxia.

Exclusion criteria

Presence of any other complication related to sickle cell disease requiring hospitalization such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, etc.
Severe anemia (hemoglobin < 5g/dL)
History of red blood cell transfusion within the last 30 days
Systemic steroid therapy within the last 48 hours
Pregnant (as confirmed by a negative 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 6 to 13 years > 0.9 mg/dL
Age 14-17 years 1.0 mg/dL
Age 18 years >1.5mg/dL
Patients with an inability to give consent will be excluded

Treatment and study plan

Intravenous citrulline

Drug

Intravenous citrulline at a bolus dose of 20 mg/kg over 5 minutes and then continuous at a rate of 7 mg/kg/hour for the next 23 hours for the first 7 participants, and depending on safety and pharmacokinetic profile, increase or decrease the continuous rate to 9 or 5 mg/kg/hour for the next 7 participants.

Primary outcomes

Number of Participants With Adverse Events

Time frame: 30 days

The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Plasma Citrulline Level

Time frame: Plasma citrulline levels will be evaluated at the following time points: trough level, 10 minutes (peak level), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours, to evaluate the pharmacokinetic profile

Sponsors and collaborators

Lead sponsor

University of Mississippi Medical Center

Other

Registry information

Official study title

A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome

Important dates

Study start: 2016
Primary completion: 2017
Study completion: 2017
First posted: Mar 3, 2016
Registry last updated: Jun 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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