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

NCT02697240 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2014-0230
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; citrulline

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (1)

Intravenous citrulline

EXPERIMENTAL

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

Drug: Intravenous citrulline

Interventions

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.

Intravenous citrulline

Eligibility Criteria

• Age: 6 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Mississippi Medical Center: lead

Study Sites (1)

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Related 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. doi: 10.1016/j.jtcvs.2007.02.043.

  PMID: 17662768 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Suvankar Majumdar
• Organization: Children's National Medical Center

smajumdar@childrensnational.org

2024763800

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: March 3, 2016
• Study Start: February 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: June 25, 2019
• Results First Posted: April 17, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)