Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy

Official Title: “Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy”

Objectives/Purpose:

To determine the safety and efficacy of a Vitamin K (Vit K) antagonist (warfarin) in treating Metachromatic Leukodystrophy (MLD).

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.

1. Duration of Treatment: 4 weeks

2. 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.

3. 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.

4. 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.

5. 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.

Intervention(s) in this Clinical Trial

• 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

Primary Measures

• Quantitative Neurological Assessment
  • Time Frame: 4 weeks
    Safety Issue?: No
• Urine Sulfatides Quantification
  • Time Frame: 4 weeks
    Safety Issue?: No

Secondary Measures

• Brain MRI
  • Time Frame: before and after treatment
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 1 Year

Maximum Age for this Clinical Trial: 10 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: The Cooper Health System Other

Overall Clinical Trial Officials and Contacts

Paola Leone, Ph.D. Study Director UMDNJ/SOM  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00683189

Study ID Number: RP#07/063

ClinicalTrials.gov Identifier: NCT00683189

Health Authority: United States: Institutional Review Board