Back to resultsA Study of Oral L-citrulline in Sickle Cell Disease
Primary Purpose
Sickle Cell Disease
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oral L-citrulline
Sponsored by
About this trial
This is an interventional diagnostic trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
- Sickle cell disease genotypes (HbSS, HbS/β-thalassemia
- HbS/β+thalassemia, HbSC)
- Patients with sickle cell disease aged 10 to 25 years old
- Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
- Patients 18 through 25 years of age who provide signed consent.
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: 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 assent (ages 10 to 17 years) or consent (ages 18 through 25 years) will be excluded
- 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
Oral citrulline
Arm Description
Outcomes
Primary Outcome Measures
Peak plasma citrulline concentration (Cmax)
Rate of citrulline appearance (Rapp)
Constant of citrulline removal (krem)
Volume of distribution
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Secondary Outcome Measures
Level of nitric oxide
Full Information
NCT ID
NCT02659644
First Posted
December 29, 2015
Last Updated
June 19, 2018
Sponsor
University of Mississippi Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02659644
Brief Title
A Study of Oral L-citrulline in Sickle Cell Disease
Official Title
A Phase I Dose-Ranging Study of Oral L-citrulline in Steady-State Sickle Cell
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Principal Investigator moved to another institution
Study Start Date
December 2015 (undefined)
Primary Completion Date
December 31, 2017 (Anticipated)
Study Completion Date
December 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Mississippi Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Sickle cell disease is a genetic red blood cell disorder that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Also, low amounts of nitric oxide can occur in sickle cell disease, a substance important for widening the blood vessel wall and therefore preventing blockage of the small blood vessels.
Citrulline is a drug that is known to increase nitric oxide. This is a phase I study of citrulline given by mouth to evaluate the safety, tolerability and appropriate dosing of this medication for individuals with 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
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral citrulline
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Oral L-citrulline
Intervention Description
There will be a total of 16 patients divided into 4 equal cohorts. The first 4 cohorts will be started on a 7 day oral regimen of twice daily L-citrulline. They will return to clinic on day #7 to evaluate nitric oxide metabolite levels and pharmacokinetic (PK) profile of citrulline. After PK analysis, the next cohort of patients will be given a higher or lower dose based on their weight and also based safety and tolerability. Of note, a PK analysis will be performed for each 4 patient cohort prior to starting citrulline for the subsequent cohort. Assessment for adverse events will be done at specified times throughout the study duration via both phone and clinic encounters.
Primary Outcome Measure Information:
Title
Peak plasma citrulline concentration (Cmax)
Time Frame
7 days
Title
Rate of citrulline appearance (Rapp)
Time Frame
7 days
Title
Constant of citrulline removal (krem)
Time Frame
7 days
Title
Volume of distribution
Time Frame
7 days
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Level of nitric oxide
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 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)
Patients with sickle cell disease aged 10 to 25 years old
Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
Patients 18 through 25 years of age who provide signed consent.
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: 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 assent (ages 10 to 17 years) or consent (ages 18 through 25 years) will be excluded
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
Plan to Share IPD
No
Citations:
PubMed Identifier
17662090
Citation
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008 Jan;65(1):51-9. doi: 10.1111/j.1365-2125.2007.02990.x. Epub 2007 Jul 27.
Results Reference
background
PubMed Identifier
17953788
Citation
Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62. doi: 10.1017/S0007114507841110. Epub 2007 Oct 22.
Results Reference
background
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A Study of Oral L-citrulline in Sickle Cell Disease
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