The Natural History of Infantile Globoid Cell Leukodystrophy

March 7, 2018 updated by: Zymenex A/S

A Longitudinal Observational Study That Will Evaluate Prospectively Clinical and Surrogate Parameters That Are Affected in Infant Patients With Globoid Cell Leukodystrophy

The purpose of this natural history study is to understand more about the progression of infantile Krabbe disease, a very rare genetic disease. There is very little published longitudinal data with only anecdotal cases. This natural history study will be important in understanding the effect of future therapies that are presently in the preclinical phase.

Study Overview

Status

Completed

Conditions

Infantile Globoid Cell Leukodystrophy

Detailed Description

Infantile globoid cell leukodystrophy (GLD, or Krabbe disease) is a rare, inherited degenerative disorder of the central and peripheral nervous systems. It is characterized by the presence of globoid cells (multinucleated cells), the breakdown of the nerve's protective myelin coating, and destruction of brain cells. Globoid cell leukodystrophy is one of a group of genetic disorders called the leukodystrophies. These disorders impair the growth or development of the myelin sheath, and causes severe degeneration of mental and motor skills. Myelin, which lends its color to the "white matter" of the brain, is a complex substance made up of a number of different glucoproteins and glucolipids, the most important of which is galactocerebroside. Each of the leukodystrophies affects one of these substances. Globoid cell leukodystrophy is caused by a deficiency of galactocerebroside ß-galactosidase (GALC), an essential enzyme for myelin metabolism. The disease most often affects infants, with onset before the age of 6 months, but can occur in adolescence or adulthood. Symptoms include irritability, unexplained fever, limb stiffness (hypertonia), seizures, feeding difficulties, vomiting, and slowing of mental and motor development. Other symptoms include muscle weakness, spasticity, deafness, and blindness.

There is no cure for globoid cell leukodystrophy. Generally, treatment for the disorder is symptomatic and supportive.

Infantile globoid cell leukodystrophy is generally fatal before age 2 years. Patients with juvenile- or adult-onset disease generally have a milder course of the disease and live significantly longer.

Globoid cell leukodystrophy is a autosomal recessive disorder with a wide geographic distribution. The incidence in the United States is estimated as 1 in 100.000 births. However, the incidence appears to be higher in the Scandinavian countries. 32 Swedish cases were reported during the period from 1953 through 1967 with calculated incidence at 1.9 per 100.000 births.

To be able to compare the benefits experienced by infants with globoid cell leukodystrophy, who receive a possible future treatment, to those untreated, a better understanding of the natural course of infantile GLD is necessary. The current literature contains only case studies of individual or small groups of GLD patients. A longitudinal study of a larger population of patients with infantile GLD has yet to be performed. This protocol is a 1.5 years longitudinal observational study to capture natural history data in patients with infantile GLD. This data will provide information on the range and diversity of clinical disease parameters that can in the future be used to evaluate treatment effects.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Pennsylvania
  - Pittsburgh, Pennsylvania, United States, 15224
    - Children's Hospital of Pittsburgh, 4401 One Children's Hospital Drive,4401 Penn Avenue

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 2 years (Child)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients will be enrolled regardless of gender, race or ethnicity. Patients will be identified through clinical referrals from other physicians or medical centers and also those patients receiving clinical care at the Program for Neurodevelopmental Function in Rare Disorders.

Description

Inclusion Criteria:

Informed consent obtained before any study-related activities. (Study-related activities are any procedure that would not have been performed during normal management of the subject)
The patient must have a documented diagnosis of infantile globoid cell leukodystrophy with galactocerebroside ß-galactosidase (GALC) activity < 0.50 nmol/h/mg protein and evidence of two pathogenic mutations in the GALC gene must be confirmed after the baseline visit
The patient must have an age at the time of screening < 2 years
The patient's parent(s) and/or legal guardian must have the ability to comply with the clinical protocol

Exclusion Criteria:

History of hematopoietic stem cell transplantation
Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition
Presence of major congenital abnormality
Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the principal investigator, would preclude participation in the study
Use of any investigational product within 30 days prior to study enrollment or currently enrolled in another study which involves clinical investigations
The patient's parent(s) and/or legal guardian is unable to understand the nature, scope, and possible consequences of the study
Patient is unable to comply with the protocol, i.e. inability to return for follow-up evaluations or otherwise unlikely to complete the study as determined by the principal investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Case-Only
Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
This longitudinal observational study will collect information on patients diagnosed with infantile globoid cell leukodystrophy over approximately an 18-month period. Time Frame: 18 month	18 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zymenex A/S

Investigators

Principal Investigator: Maria L Escolar, MD, NFRD Office, Pittsburgh, Pennsylvania, US

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

September 23, 2009

First Submitted That Met QC Criteria