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

NCT ID: NCT02697240

Last Updated: 2019-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-04-30

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.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous citrulline

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

Group Type: EXPERIMENTAL

Intravenous citrulline

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Mississippi Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Suvankar Majumdar

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Mississippi Medical Center

Jackson, Mississippi, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17662768 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-0230

Identifier Type: -

Identifier Source: org_study_id