A Study of Oral L-citrulline in Sickle Cell Disease

Sponsor

University of Mississippi Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02659644

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Sickle cell disease is a genetic red blood cell disorder that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Also, low amounts of nitric oxide can occur in sickle cell disease, a substance important for widening the blood vessel wall and therefore preventing blockage of the small blood vessels.

Citrulline is a drug that is known to increase nitric oxide. This is a phase I study of citrulline given by mouth to evaluate the safety, tolerability and appropriate dosing of this medication for individuals with sickle cell disease.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Oral L-citrulline	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

A Phase I Dose-Ranging Study of Oral L-citrulline in Steady-State Sickle Cell

Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Dec 31, 2017

Actual Study Completion Date :

Dec 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral citrulline	Drug: Oral L-citrulline There will be a total of 16 patients divided into 4 equal cohorts. The first 4 cohorts will be started on a 7 day oral regimen of twice daily L-citrulline. They will return to clinic on day #7 to evaluate nitric oxide metabolite levels and pharmacokinetic (PK) profile of citrulline. After PK analysis, the next cohort of patients will be given a higher or lower dose based on their weight and also based safety and tolerability. Of note, a PK analysis will be performed for each 4 patient cohort prior to starting citrulline for the subsequent cohort. Assessment for adverse events will be done at specified times throughout the study duration via both phone and clinic encounters.

Arm

Intervention/Treatment

Experimental: Oral citrulline

Drug: Oral L-citrulline

There will be a total of 16 patients divided into 4 equal cohorts. The first 4 cohorts will be started on a 7 day oral regimen of twice daily L-citrulline. They will return to clinic on day #7 to evaluate nitric oxide metabolite levels and pharmacokinetic (PK) profile of citrulline. After PK analysis, the next cohort of patients will be given a higher or lower dose based on their weight and also based safety and tolerability. Of note, a PK analysis will be performed for each 4 patient cohort prior to starting citrulline for the subsequent cohort. Assessment for adverse events will be done at specified times throughout the study duration via both phone and clinic encounters.

Outcome Measures

Primary Outcome Measures

Peak plasma citrulline concentration (Cmax) [7 days]
Rate of citrulline appearance (Rapp) [7 days]
Constant of citrulline removal (krem) [7 days]
Volume of distribution [7 days]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [7 days]

Secondary Outcome Measures

Level of nitric oxide [7 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sickle cell disease genotypes (HbSS, HbS/β-thalassemia
HbS/β+thalassemia, HbSC)
Patients with sickle cell disease aged 10 to 25 years old
Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
Patients 18 through 25 years of age who provide signed consent.

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: Age 6 to 13 years > 0.9 mg/dL, Age 14-17 years 1.0 mg/dL, Age >18 years >1.5mg/dL
Patients with an inability to give assent (ages 10 to 17 years) or consent (ages 18 through 25 years) will be excluded
History of diabetes due to risk of electrolyte imbalance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216

Sponsors and Collaborators

University of Mississippi Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Suvankar Majumdar, Associate Professor, University of Mississippi Medical Center

ClinicalTrials.gov Identifier:

NCT02659644

Other Study ID Numbers:

2015-0191

First Posted:

Jan 20, 2016

Last Update Posted:

Jun 21, 2018

Last Verified:

Jun 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Anemia, Sickle Cell

Study Results

No Results Posted as of Jun 21, 2018