Back to resultsA Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease
Primary Purpose
Sickle Cell Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intravenous (IV) citrulline
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
- Sickle cell disease genotypes (HbSS, HbS/β° thalassemia, HbS/β+thalassemia, HbSC)
Exclusion Criteria:
- Presence of any acute illness defined by fever >100.4° F within the past 48 hours
- Presence of sickle cell pain crisis defined by the presence of pain requiring oral or parental opioid therapy.
- Presence of acute chest syndrome or 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, and patients with diabetes etc.
- Severe anemia (hemoglobin < 5g/dL)
- History of red blood cell transfusion within the last 14 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.
- Elevated serum creatinine >1.5mg/dL
- Patients with an inability to give consent will be excluded
- Medications that are known to be contra-indicated with use of L-citrulline (concurrent use of hydroxyurea will be allowed).
- History of diabetes due to risk of electrolyte imbalance
Sites / Locations
- University of Mississippi Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IV citrulline
Arm Description
IV citrulline 20 mg/kg bolus with dose escalation of 10 mg/kg to target citrulline concentration of 100 µmol/L with a maximum dose of 60 mg/kg.
Outcomes
Primary Outcome Measures
Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02314689
Brief Title
A Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Suvankar Majumdar
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the maximum tolerated dose, safety and pharmacokinetics of an investigational drug, intravenous (IV) citrulline, in subjects in steady-state sickle cell disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
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
IV citrulline
Arm Type
Experimental
Arm Description
IV citrulline 20 mg/kg bolus with dose escalation of 10 mg/kg to target citrulline concentration of 100 µmol/L with a maximum dose of 60 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Intravenous (IV) citrulline
Primary Outcome Measure Information:
Title
Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Sickle cell disease genotypes (HbSS, HbS/β° thalassemia, HbS/β+thalassemia, HbSC)
Exclusion Criteria:
Presence of any acute illness defined by fever >100.4° F within the past 48 hours
Presence of sickle cell pain crisis defined by the presence of pain requiring oral or parental opioid therapy.
Presence of acute chest syndrome or 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, and patients with diabetes etc.
Severe anemia (hemoglobin < 5g/dL)
History of red blood cell transfusion within the last 14 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.
Elevated serum creatinine >1.5mg/dL
Patients with an inability to give consent will be excluded
Medications that are known to be contra-indicated with use of L-citrulline (concurrent use of hydroxyurea will be allowed).
History of diabetes due to risk of electrolyte imbalance
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
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.
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A Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease
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