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

NCT02314689 | Completed Phase 1 Results DMC

• 1 other identifier: SCD-124700.
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria

  12 months

Study Arms (1)

IV citrulline

EXPERIMENTAL

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

Interventions

Intravenous (IV) citrulline DRUG

IV citrulline

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Sickle cell disease genotypes (HbSS, HbS/β° thalassemia, HbS/β+thalassemia, HbSC)

You may not qualify if:

• 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

Sponsors & Collaborators

• Suvankar Majumdar: lead

Study Sites (1)

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Related Publications (1)

• 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.

  PMID: 17662768 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Suvankar Majumdar MD
• Organization: University of Mississippi Medical Center

smajumdar@umc.edu

6019845220

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 11, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 3, 2019
• Results First Posted: March 7, 2016

Record last verified: 2019-07

Locations

US (1)