Clinical trial NCT01963650: Natural History Study of Children With Metachromatic Leukodystrophy
Official title: Natural History Study of Children With Metachromatic Leukodystrophy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Lipid Metabolism Disorders
Metachromatic Leukodystrophy (MLD)
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Sphingolipidoses
Hereditary Central Nervous System Demyelinating Diseases
Metabolic Inborn Brain Diseases
Lysosomal Storage Diseases
Metabolic Diseases
Sulfatidosis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-10-16
Enrollment: 1
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll up to 30 male or female children (\<12 years of age) with a confirmed MLD diagnosis.

Brief summary: The purpose of this study is evaluate the natural course of disease progression related to gross motor function in children with metachromatic leukodystrophy (MLD).

Detailed description: Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A (ASA). MLD is a rare genetic disease that occurs in most parts of the world. The estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births.

This study is a multicenter, observational, longitudinal study that plans to enroll up to 30 patients with onset of MLD-related signs and symptoms prior to 30 months of age and who are less than 12 years of age. Patients will participate in this study for approximately 114 weeks (Screening through Follow-up) and will be assessed at defined intervals for disease status.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of MLD by both:

   * arylsulfatase A (ASA) deficiency by assay in leukocytes AND
   * elevated sulfatide in urine
2. Appearance of the first symptoms of disease at or before 30 months of age.
3. A GMFM-88 total (percent) score greater than or equal to 40 at the screening examination.
4. The patient is less than 12 years of age at the time of enrollment.
5. The patient and his/her parent or legally authorized representative(s) must have the ability to comply with the clinical protocol.
6. Patient's parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the patient.

Exclusion Criteria:

1. History of hematopoietic stem cell transplantation.
2. The patient has any known or suspected hypersensitivity to agents used for anesthesia or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions.
3. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study.
4. The patient is enrolled in another clinical study that involves the use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.

Primary outcomes:
measure: The primary endpoint of this study is the change from baseline in motor function using the GMFM-88 total (percent) score.
timeFrame: Week 0 to Week 104
Secondary outcomes:
measure: The change from baseline in ability to swallow as assessed by the Functional Endoscopic Evaluation of Swallowing.
timeFrame: Week 0 to Week 104
measure: The change from baseline in nerve conduction as measured by the electroneurography.
timeFrame: Week 0 to Week 104
measure: The change from baseline in the adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales.
timeFrame: Week 0 to Week 104
measure: The change from baseline in domain-specific Caregiver Observed MLD Functioning and Outcomes Reporting Tool.
timeFrame: Week 0 to Week 104
measure: The change from baseline in cognitive function using the Mullen Scales of Early Learning.
timeFrame: Week 0 to Week 104
measure: Reporting of any study procedure-related nonserious AEs and/or any SAEs
timeFrame: Week 0 to Week 114
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor UCLA Pediatrics
state: California
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Pittsburgh
country: United States
facility: Children's Hospital Of Pittsburgh
state: Pennsylvania
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA) (University Hospital Antwerpen)
city: Porto Alegre
country: Brazil
facility: Hospital de Cllnicas de Porto Alegre (HCPA) / UFRGS
city: Westmount
country: Canada
facility: Montreal Children's Hospital
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Le Kremlin Bicêtre
country: France
facility: Hôpital De Bicêtre
city: Tubingen
country: Germany
facility: Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin
city: Osaka
country: Japan
facility: Faculty Of Medicine, Osaka University Graduate School Of Medicine
city: Tokyo
country: Japan
facility: The Jikei University School Of Medicine - Institute Of Dna Medicine
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Onkoloji Hastanesi
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: