Clinical trial NCT00683189: Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy
Official title: Effect of Warfarin in the Treatment of Metachromatic Leukodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metachromatic Leukodystrophy
Keywords: MLD
Lead sponsor: The Cooper Health System
Sponsor class: OTHER
First posted: 2008-05-23
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objectives/Purpose:

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Quantitative Neurological Assessment
timeFrame: 4 weeks
measure: Urine Sulfatides Quantification
timeFrame: 4 weeks
Secondary outcomes:
measure: Brain MRI
timeFrame: before and after treatment
Other outcomes:
Locations:
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
Study officials:
affiliation: UMDNJ/SOM
name: Paola Leone, Ph.D.
role: STUDY_DIRECTOR
affiliation: The Cooper Health System
name: Mitra Assadi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: