A Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Intravenous (IV) citrulline

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV citrulline; 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.	Drug: Intravenous (IV) citrulline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria	12 months

Collaborators and Investigators

• Sponsor: Suvankar Majumdar

Publications and helpful links

General 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. doi: 10.1016/j.jtcvs.2007.02.043.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 11, 2014

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: SCD-124700.