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

Phase 1

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: Intravenous citrulline

• Registration Number: NCT02697240
• Lead Sponsor: University of Mississippi Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-29
• Study First Submitted QC: 2016-02-29
• Study First Posted: 2016-03-03
• Primary Completion: 2017-04
• Study Completion: 2017-04
• Results First Submitted: 2018-06-19
• Results First Submitted QC: 2019-04-15
• Results First Posted: 2019-04-17
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-17
• Last Update Posted: 2019-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. Sickle cell disease genotypes (HbSS, HbS/β0-thalassemia, HbS/β+-thalassemia, HbSC)
2. Ages 6 to 50 years old
3. 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
4. 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

1. 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.

2. Severe anemia (hemoglobin < 5g/dL)

3. History of red blood cell transfusion within the last 30 days

4. Systemic steroid therapy within the last 48 hours

5. Pregnant (as confirmed by a negative urine pregnancy test) or lactating female

6. Alanine/aspartate transferase >2x upper limit of normal laboratory range for age.

7. 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

8. Patients with an inability to give consent will be excluded

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intravenous citrulline	Intravenous citrulline	Intravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	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	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

Trial Locations

Locations (1)

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States