Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02697240
Recruitment Status : Completed
First Posted : March 3, 2016
Results First Posted : April 17, 2019
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Suvankar Majumdar, University of Mississippi Medical Center

Tracking Information
First Submitted Date  ICMJE February 29, 2016
First Posted Date  ICMJE March 3, 2016
Results First Submitted Date  ICMJE June 19, 2018
Results First Posted Date  ICMJE April 17, 2019
Last Update Posted Date June 25, 2019
Study Start Date  ICMJE February 2016
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 29, 2016)
  • 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: 48 hours ]
    Plasma citrulline levels will be evaluated at certain time points to evaluate the pharmacokinetic profile of continuous intravenous citrulline
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
Official Title  ICMJE A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Intravenous citrulline
Intravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours.
Intervention: Drug: Intravenous citrulline
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 15, 2019)
4
Original Estimated Enrollment  ICMJE
 (submitted: February 29, 2016)
14
Actual Study Completion Date  ICMJE April 2017
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02697240
Other Study ID Numbers  ICMJE 2014-0230
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Suvankar Majumdar, University of Mississippi Medical Center
Study Sponsor  ICMJE University of Mississippi Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Mississippi Medical Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP