This trial has been completed. To the best of our knowledge no efficacy was demonstrated.
January 31, 2008
DISCLAIMER - this information is provided at the request of the study coordinators. It is for informational purposes only and should not be considered, and is not, an endorsement by MLD Foundation. Consult your personal physician before considering involvement in this or any study or clinical trial.
Substrate Reduction Research Study
MLD Foundation has been asked to share information about a substrate reduction therapy research study investigating the affects of warfarin, which is commonly used as a blood thinner, in children affected by MLD. Participants will be tested for changes in their MRI scan, motor function, and for measurable reductions of sulfatides in their urine.
The researchers are currently recruiting patients for this study.
With MLD there is not enough ARSA enzyme present to break down all of the sulfatides produced by the body. Instead of increasing the enzyme levels, which is the goal of most other MLD therapies, substrate reduction therapy focuses on reducing the amount of sulfatide produced by the body. This therapy may be effective when there is a low level of enzyme being produced, which is the case for many affected with MLD. If you are producing no enzymes then this therapy will be less effective.
Warfarin is the generic name for Coumadin, a drug which is FDA approved and most commonly known for its use as a drug to thin blood and reduce the potential for blood clots.
It is known Vitamin K has an essential role in the biosynthesis of sulfatides and other sphingolopids in the brain and the rest of the body. Administering warfarin, a Vitamin K antagonist, may reduce the amount of sulfatides stored in myelin containing cells, oligodendroglia or schwann cells. If this therapy works in those affected by MLD it will not eliminate MLD, rather it would reduce the negative affects of MLD by reducing the sulfatide levels and the resulting buildup.
This study is an investigational treatment. Investigational means that the drug is still being tested for treatment of MLD. Warfarin is approved by the Federal Drug Administration (FDA) for treatment of clotting disorders and preventing blood clots in adults and children.
It is not known if warfarin is effective in children with MLD. The purpose of this study is to find out if this investigational approach has positive results in children with MLD and to see if there are unanticipated side affects with MLD compromised children.
Four Italian children have already participated in this study with no adverse affects reported by the study team. These children remain on warfarin for longer term study. The early results were mixed with no consistent reduction in sulfatides noted. An additional six children are being sought to participate in and complete the study.
Who may or may not take part in this study?
To be included in this study, your child must show the following characteristics:
- Be 2 to 7 years of age with a confirmed MLD diagnosis
- Show evidence for neurological and developmental decline documented over the past 6 months
- Received and failed bone marrow transplantation (BMT) or be excluded from a BMT treatment due to delayed diagnosis or any other reasons.
Your child might be excluded from the study due to one of the following reasons:
- Any Children with MLD who are eligible for and might receive a BMT.
- Any Children with MLD who suffer with a bleeding disorder, moderate to severe anemia or any other hematological disorders.
- Any other contraindications for using warfarin.
How long will the study take and what is involved?
The study formally lasts six weeks. A GMFM (gross motor/fine motor skills) test and a MRI are done at the beginning of the study and repeated at the end of the study. Various regular tests will be necessary during the study including urine testing for sulfatide levels and close monitoring of the warfarin levels in the blood.
The study is being run at a NE medical center. You need to go to this NE medical center at the beginning and end of the study, however, if your local doctors, specifically we are recommending a hematologist, will commit to very regular monitoring of your warfarin levels, you may return home during the interim. The monitoring is critical to the safety of your child - your doctors may not want to do this monitoring or may be prohibited by the lack of a local IRB (Institutional Review Board) approval. This is one of the reasons we are asking your doctors to contact us for study information (see below).
The researchers expect your insurance to cover many of the testing expenses - you should confirm this before you start the study.
MLD Foundation has an information packet discussing concerns expressed by our medical resources about we perceive to be serious safety, efficacy, and trial design risks of this clinical trial that we would like to provide to your local family medical team. Please contact us to make these arrangements.
The details of the trial can be found on ClinicalTrials.gov
Dean Suhr ... 503-656-4808 or email: warfarin@MLDfoundation.org