Hydoxycarbamide and L-Carnitine Therapy in Sickle Cell Anemia

Study Overview
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Brief Summary
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The role of the combination therapy of hydroxyurea and L-Carnitine was studied in thalassemic patients. nevertheless its role in sickle cell anemia patients was not investigated

Detailed Description
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Sickle cell disease (SCD) is a common monogenic disorder affecting over 100,000 people in the United States alone, and millions more worldwide. This often devastating disease is characterized by red blood cell (RBC) sickling; chronic hemolytic anemia; episodic vaso-occlusion associated with severe pain and inflammation; acute and cumulative organ damage that manifests as stroke, acute chest syndrome, sickle lung disease, pulmonary hypertension nephropathy and end-stage renal disease; and other chronic morbidities. Lives of patients with SCD are characterized by frequent episodes of severe pain (vaso-occlusive events or crises); acute organ dysfunction, including a pneumonia-like syndrome termed acute chest syndrome, and strokes starting in childhood; and progressive multi-organ damage. Not surprisingly, patients with SCD have very high health care utilization (over $1 billion/year in healthcare costs in the United States alone, and a median life-expectancy of only  45-58 years, compared to the life expectancy of 78.2 years overall in the United States. Although it is licensed in the United States for administration to sickle cell patients who have ≥ 3 crises a year in steady state, hydroxyurea (HU) remains unlicensed in most countries where it is regarded as an experimental drug In those areas, where HU is unlicensed for SCD, it is offered to patients who have ≥ 5 crises a year; or 3-4 crises a year with either neutrophil count ≥ 10 × 109/L or platelet count ≥ 500 × 109/L in steady state ; bearing in mind that the reference range for neutrophil count in black people is 1-3 × 109/L, and is 100-300 × 109/L for platelets . Since high neutrophil count in steady state is a marker of severe SCD , these criteria usually identify individuals who have a clinical course sufficiently severe to ensure that the benefits of hydroxyurea therapy justify the potential risks. HU therapy is offered if the patient does not want to have (more) children, and is weighed against any severe impairment of liver or kidney function, or blood cytopenia. HU is unlicensed in most countries because the long-term adverse effects are unknown, not because the clinical efficacy is in doubt. In fact, after over 9 years of follow-up, HbSS subjects who received HU in the US placebo-controlled trial, had significantly less painful crises, acute chest syndrome, and mortality . Potential long-term toxic effects that reduce enthusiasm for HU include teratogenicity, carcinogenesis and, for young children, impaired cognitive development.

Official Title
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Treatment With Hydoxycarbamide and L-Carnitine in Adult Patients With Severe Forms of Sickle Cell Anemia: An Overview

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine
* Drug: Hydroxycarbamide 500 Mg Oral Capsule
* Drug: L-Carnitine, 250 Mg Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with sickle cell disease Not welling for pregnancy in females or to father a baby in males Frequent episodes Non-compliance to transfusion Exclusion Criteria: <18 years Hypersensitivity to hydroxycarbamide or L-Carnitine Pregnancy Other chronic infection or inflammation

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Non-randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydra+L-Carnitine<br>Hydroxycarbamide+ L-Carnitine+supportive treatment | Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine<br>* Combination therapy<br>* Other names: Hydroxyurea+LC;|
| Active Comparator: Hydra only<br>Hydroxycarbamide+ supportive treatment | Drug: Hydroxycarbamide 500 Mg Oral Capsule<br>* Single agent<br>* Other names: Hydroxyurea;|
| Active Comparator: L-Carnitine only<br>L-Carnitine+ supportive treatment | Drug: L-Carnitine, 250 Mg Oral Capsule<br>* single agent<br>* Other names: L-Carnitine;|
| No Intervention: Supportive measures<br>Supportive only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological(HR) | Change of hemoglobin | 2-3 months | 
| Hematological response | Change of hematocrit | 2-3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of painful episodes/ blood transfusions | Change of frequency of painful episodes and blood transfusion | 1-year |