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

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intravenous citrulline
Sponsored by
University of Mississippi Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, citrulline

Eligibility Criteria

6 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Mississippi Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intravenous citrulline

Arm Description

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

Outcomes

Primary Outcome Measures

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)
Plasma Citrulline Level

Secondary Outcome Measures

Full Information

First Posted
February 29, 2016
Last Updated
June 17, 2019
Sponsor
University of Mississippi Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02697240
Brief Title
A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
Official Title
A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
April 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Mississippi Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
sickle cell disease, citrulline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous citrulline
Arm Type
Experimental
Arm Description
Intravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours.
Intervention Type
Drug
Intervention Name(s)
Intravenous citrulline
Intervention Description
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 Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame
30 days
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17662768
Citation
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.
Results Reference
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A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome

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