Natural History Study of Children With Metachromatic Leukodystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by Shire
Information provided by (Responsible Party):
Shire Identifier:
First received: October 11, 2013
Last updated: December 9, 2015
Last verified: December 2015
The purpose of this study is evaluate the natural course of disease progression related to gross motor function in children with metachromatic leukodystrophy (MLD).

Lipid Metabolism, Inborn Errors
Central Nervous System Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Metabolic Diseases
Nervous System Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lipid Metabolism Disorders
Leukodystrophy, Metachromatic
Demyelinating Diseases

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Children With Metachromatic Leukodystrophy

Resource links provided by NLM:

Further study details as provided by Shire:

Primary Outcome Measures:
  • The primary endpoint of this study is the change from baseline in motor function using the GMFM-88 total (percent) score. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change from baseline in ability to swallow as assessed by the Functional Endoscopic Evaluation of Swallowing. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
  • The change from baseline in nerve conduction as measured by the electroneurography. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
  • The change from baseline in the adaptive behavior composite standard score as measured by the Vineland Adaptive Behavior Scales. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
  • The change from baseline in domain-specific Caregiver Observed MLD Functioning and Outcomes Reporting Tool. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
  • The change from baseline in cognitive function using the Mullen Scales of Early Learning. [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
  • Reporting of any study procedure-related nonserious AEs and/or any SAEs [ Time Frame: Week 0 to Week 114 ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA
Sample for genotype testing is collected and any remaining sample is retained for follow up or repeat testing. The sample is not retained for unspecified additional testing.

Estimated Enrollment: 30
Study Start Date: December 2013
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
No treatment

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.


Ages Eligible for Study:   up to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01963650

Contact: Margaret Wasilewski, MD 1-781-266-3326

United States, California
Harbor UCLA Pediatrics Recruiting
Torrance, California, United States, 90502
Contact: Nathalia Cressey    310-222-3756   
United States, District of Columbia
Children's National Health System Recruiting
Washington, District of Columbia, United States, 20010
Contact: Amy Pizzino    202-476-6230   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Barbara Burton, MD    312-227-6120   
United States, Pennsylvania
Children's Hospital Of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Maria Escolar, MD    412-692-9955   
Hospital Universitario Austral Recruiting
Pilar, Argentina, B1629ODT
Contact: Hernan Amartino, MD    54 911 49475492   
Universitair Ziekenhuis Antwerpen (UZA) (University Hospital Antwerpen) Recruiting
Edegem, Belgium, 2650
Contact: François Eyskens, Prof, Dr   
Hospital de Cllnicas de Porto Alegre (HCPA) / UFRGS Not yet recruiting
Porto Alegre, Brazil, 90035-003
Contact: Roberto Giugliani, MD    555199945003   
Montreal Children's Hospital Recruiting
Westmount, Canada, H3Z 2Z3
Contact: Luan Tran, MD    514-934-1934 ext 23380   
Fundacion Cardiofantil Withdrawn
Bogota, Colombia
Copenhagen University Hospital, Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Christine Dali, MD    4525229155   
Hôpital De Bicêtre Not yet recruiting
Le Kremlin Bicêtre, France, 94275
Contact: Caroline Sevin, MD    33661778475   
Univesitatsklinikum Tubingen Klinik fur Kinder und Jugendmedizin Not yet recruiting
Tubingen, Germany, 72076
Contact: Samuel Groschel, MD    4915209061667   
Tel Aviv Sourasky Medical Center Withdrawn
Tel Aviv, Israel, 64239
Faculty Of Medicine, Osaka University Graduate School Of Medicine Recruiting
Osaka, Japan, 565-0871
Contact: Norio Sakai, MD, PhD   
The Jikei University School Of Medicine - Institute Of Dna Medicine Not yet recruiting
Tokyo, Japan, 105-8461
Contact: Toya Ohashi, MD   
Hacettepe Universitesi Tip Fakultesi Onkoloji Hastanesi Recruiting
Ankara, Turkey, 6100
Contact: Meral Topcu, MD   
Sponsors and Collaborators
Study Director: Margaret Wasilewski, MD Shire
  More Information

No publications provided

Responsible Party: Shire Identifier: NCT01963650     History of Changes
Other Study ID Numbers: HGT-MLD-092 
Study First Received: October 11, 2013
Last Updated: December 9, 2015
Health Authority: Argentina: National Committee of Ethics in Science and Technology
Germany: Ethics Commission
Canada: Ethics Review Committee
Brazil: Ministry of Health
France: Ethics Committee
Denmark: Ethics Committee
Turkey: Ethics Committee
United States: Institutional Review Board
Japan: Japanese Pharmaceuticals and Medical Devices Agency
Belgium: Institutional Review Board

Additional relevant MeSH terms:
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Leukodystrophy, Metachromatic
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases processed this record on February 11, 2016