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

Phase 1

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: Intravenous (IV) citrulline

• Registration Number: NCT02314689
• Lead Sponsor: Suvankar Majumdar

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-12-05
• Study First Submitted QC: 2014-12-10
• Study First Posted: 2014-12-11
• Study Start: 2015-01
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Results First Submitted: 2015-12-09
• Results First Submitted QC: 2016-03-04
• Results First Posted: 2016-03-07
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-30
• Last Update Posted: 2019-09-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IV citrulline	Intravenous (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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria	12 months

Trial Locations

Locations (1)

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States