Clinical trial NCT02697240: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
citrulline
Lead sponsor: University of Mississippi Medical Center
Sponsor class: OTHER
First posted: 2016-03-03
Enrollment: 4
Sex: ALL
Minimum age (years): 6
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 30 days
measure: Plasma Citrulline Level
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
Study officials:
References:
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.