Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy

Study Overview
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Brief Summary
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Objectives/Purpose: To determine the safety and efficacy of a Vitamin K (Vit K) antagonist (warfarin) in treating Metachromatic Leukodystrophy (MLD).

Detailed Description
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Hypothesis: Vit K has an essential role in biosynthesis of sulfatides and other sphingolopids in the brain. Administering warfarin, a Vit K antagonist, may ameliorate the phenotype in MLD by decreasing t he amount of sphingolipid storage in the neuronal cells. Study Design Prospective: we will enroll eligible consenting subjects into the study. The study will not include a control group and the families and treating physicians are informed administration of the drug. Duration of Treatment: 4 weeks Pharmacological Intervention: The patients will receive warfarin 1.5 mg at the beginning of the study period. The dosage then will be adjusted to the INR values on weekly basis. Clinical evaluation: The patients will undergo clinical assessment prior to starting the treatment and at the end of the treatment period. The clinical assessment will also include administration of Gross Motor Function Measure (GMFM), a clinical toll for evaluation of motor development in children. Urine Sulfatide Quantification: Urine samples for quantification of the sulfatide level will be collected at the time of enrollment, after 2 weeks and at the end of treatment period. Blood Monitoring: The patients will undergo blood test for PT/INR at baseline and afterwards, at weekly bases for 4 weeks. The INR will be kept in a safe range of 2-2.5. If the INR is greater than 4.0 the dosage of warfarin will be lowered and another blood draw will be performed in 3 days.

Official Title
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Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy

Conditions
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Metachromatic Leukodystrophy

Intervention / Treatment
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* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with MLD, 1 to 10 years of age who have received and failed bone marrow transplantation or are excluded from the treatment due to delayed diagnosis or any other reasons. Exclusion Criteria: Any Children with MLD who are eligible for and might receive ABMT. Any Children with MLD who suffer with a bleeding disorder, moderate to severe anemia or any other hematological disorders. Any contraindications systemic for anti-coagulation

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Warfarin|Oral administration (QD), variable dosage: patients will undergo blood test for PT/INR at baseline and afterwards, at weekly bases for 4 weeks. The INR will be kept in a safe range of 2-2.5|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Neurological Assessment |  | 4 weeks | 
| Urine Sulfatides Quantification |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain MRI |  | before and after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MLD