L-Arginine and Sickle Cell Disease

Study Overview
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Brief Summary
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One of the main problems in sickle cell disease is the decreased bioavailability of nitric oxide and arginine. This study was designed to assess if treating sickle cell disease patients with L-arginine would improve pulmonary arterial pressure and other aspects.

Detailed Description
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This is a phase III, randomized, double-blind, placebo-controlled clinical trial with sickle cell disease patients older than 1 year of age. The patients were randomly assigned to take 0.1 g/kg/day of either L-arginine or placebo orally. Adverse events were monitored by a safety committee. The variables were assessed while patients were in remission, as part of their routine care: weight, blood pressure, full blood cell count, creatinine and dosage of methemoglobin at baseline and at each follow-up visit. Peripheral oxygen saturation (SpO2), fetal hemoglobin, lactate dehydrogenase and tricuspid regurgitant jet velocity were measured through transthoracic Doppler echocardiogram before and after treatment.

Official Title
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A Randomized, Controlled, Double-blind Clinical Trial of L-arginine as Adjuvant Therapy for Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: L-arginine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of sickle cell disease confirmed through hemoglobin electrophoresis Genotypes SS, SC and Sβ thalassemia Age > 1 year Exclusion Criteria: Liver dysfunction (alanine aminotransferase ALT > 3 times the normal levels Renal dysfunction (creatinine > twice the normal levels) Increase in methemoglobin levels (> 5 times the normal levels) History of recent stroke (< 1 month) and priapism Pregnancy Allergy to L-arginine Use of sildenafil, calcium channel blockers, nitroglycerin or other nitrates

Ages Eligible for Study
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Minimum Age: 1 Year

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-arginine<br>0.1g/kg/day for 6 months | Drug: L-arginine<br>* L-arginine was administered orally at a dose of 0.1g/kg/day during 6 months.<br>Drug: Placebo<br>* Mannitol was administered orally at a dose of 01 g/kg/day for six months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tricuspid regurgitant jet velocity >2.5 m/s | Tricuspid regurgitant jet velocity was used to assess pulmonary arterial hypertension before and after treatment with L-arginine. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate dehydrogenase levels | The effect of L-argigine administration on hemolysis was assessed through the variation of serum levels of lactate dehydrogenase. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, L-arginine, hemolysis, nitric oxide, pulmonary arterial hypertension