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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02697240
• Other study ID #: 2014-0230
• Status: Completed
• Phase: Phase 1
• Start date: February 2016
• Est. completion date: April 2017

Study information

• Verified date: June 2019
• Source: University of Mississippi Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Sickle cell disease genotypes (HbSS, HbS/ß0-thalassemia, HbS/ß+-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

Related Conditions & MeSH terms

• Acute Chest Syndrome
• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Intravenous citrulline
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.

Locations

Country	Name	City	State
United States	University of Mississippi Medical Center	Jackson	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
University of Mississippi Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)	30 days
Primary	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