Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT00639132 |
Other study ID # |
NH-US |
Secondary ID |
|
Status |
Withdrawn |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 11, 2008 |
Est. completion date |
February 1, 2022 |
Study information
Verified date |
May 2024 |
Source |
University of Pittsburgh |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
There have not been longitudinal studies which track patients' neurologically or
developmentally in a systematic manner. By simultaneously tracking patients' neurodevelopment
along with neuroimaging and neurophysiologic studies it becomes much easier to draw
conclusions on the differential effects of the disease process and any available treatments
that patients might receive. In addition, many of the gene mutations, which cause MLD have
not been linked to the age of onset or the expected disease course.
Description:
Metachromatic leukodystrophy (MLD), an autosomal recessively inherited lysosomal storage
disorder, causes a deficiency of arylsulfatase A. This results in accumulation of sulfated
glycolipids (sulphatide) within lysosomes of myelin forming cells in the central and
peripheral nervous system and to a lesser extent in lysosomes of cells comprising the liver,
kidneys, and gallbladder. The disease is characterized by progressive demyelination with wide
variability in clinical onset and severity. Depending upon the age at onset and disease
progression, MLD may be classified as late infantile (6 months to 4 years), early juvenile (4
to 6 years), late juvenile (6 to 16 years), and adult (>16 years). In the late infantile and
early juvenile forms, blindness, gait disturbances, loss of speech, loss of hearing, and
quadriparesis are common signs. In older children and adults the disease may present with
gait disturbances, mental regression, and behavioral abnormalities. Disease progression, also
variable, results in death within a few years to several decades; however, disease
progression among affected siblings seems to follow a similar course, unlike many other
leukodystrophies.
Bone marrow transplantation (BMT) has been the only partially effective treatment reported
for MLD. BMT has been shown to halt disease progression when asymptomatic patients achieve
engraftment prior to the age at which symptoms occurred in an affected, symptomatic sibling.
Despite stabilization of the clinical course when receiving BMT before symptoms, patients'
neurophysiologic test abnormalities persist. The clinical implication of this finding has not
been further researched. Patients who show mild to moderate progression of their disease
prior to transplantation continue to exhibit disease progression to severe impairment.
However, specific degrees of clinical impairment in neurodevelopmental function have not been
monitored to determine what level of cognitive and motor impairment can be present and still
allow the patient to confer benefits from treatment. Patients with late infantile MLD appear
to benefit the least from the transplantation process based on preliminary unpublished data.
Several case report studies for patients with late infantile MLD indicate delayed, but
continued progression of the disease despite BMT, while others suggest initial deterioration
followed by stabilization.
Transplantation with allogenic hematopoietic stem cells has been shown to positively
influence the disease progression of other lysosomal storage diseases such as Hurler Syndrome
and Krabbe Disease and testing for enzyme replacement for MLD is already underway. For future
researchers to be able compare the benefits of children with MLD who receive treatment to
those who remained untreated, a better understanding of the natural progression of late
infantile MLD is necessary. The current literature contains studies of individual or small
groups of MLD patients that tracked intelligence quotients and neurophysiologic function, but
did not correlate this with patients' neurodevelopment. A longitudinal study of a larger
population of patients with late infantile MLD has yet to be performed. This protocol is a
longitudinal observational study to capture natural history data in patients with late
infantile MLD. This data will provide baseline neurobehavioral, neuroimaging, and
neurophysiological information that can in the future be used to evaluate treatment effects.