PK and PD Responses to Oral L-Citrulline in Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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To evaluate PK and PD responses to L-citrulline given orally for four weeks to patients with sickle cell disease who are otherwise healthy.

Detailed Description
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Phase 1, single center, open label, multiple-dose study consisting of a screening period followed by four weeks of treatment. At least 12 male and female patients, 10 years of age or older, with sickle cell disease but otherwise healthy, will be enrolled in the study. PK measurements include plasma concentrations of L-citrulline, L-arginine, L-ornithine, and L-proline following the first dose of orally administered L-citrulline and after four weeks of twice daily administration of the drug. PD measurements include intercellular and vascular adhesion molecules (ICAM, VCAM, and E-selectin), surrogate markers of sickle cell disease activity, and PAT, a measurement of vascular function.

Official Title
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Phase 1 Pharmacokinetic and Pharmacodynamic Responses to Oral L-Citrulline in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: L-citrulline tablets, 1000 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 10 years of age or older on the day of dosing, and generally healthy as determined by medical history, physical examination, and laboratory test values Diagnosis of sickle cell anemia (Hb SS) For female of child-bearing potential, a negative serum pregnancy test and using an adequate method of contraception Has signed and received a copy of the written informed consent form approved by the investigator's Institutional Review Board (IRB), understands the purposes and risks of the study and agrees to follow the restrictions and schedule of procedures as defined by this protocol Exclusion Criteria: History of sickle-cell-related pain crisis within two weeks of study Pregnant or breast feeding Transfusion within last 90 days Creatinine >1.5 X upper limit of normal SGPT > 2 X upper limit of normal History of allergic reaction to arginine or citrulline product Requires chronic medication other than study drug that cannot be discontinued during the study period Unable to take or tolerate oral medications Unreliable venous access Noncompliant with regular care Participation in an investigational drug or medical device study within previous 30 days In the opinion of the investigator is not a good candidate for participation in the study

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: L-citrulline tablets, 1000 mg|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK and PD responses to L-citrulline |  |  | 
| Endpoints will be determined as change from baseline |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety and tolerability of L-citrulline, |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease