Krabbe Disease Global Patient Registry

Krabbe Disease Clinical Trial

Official title:

The Institute for Myelin and Glia Exploration's Clinical Database of Patients With Krabbe Disease, A World-Wide Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02993796
• Other study ID #: RDCRN6726
• Secondary ID: 1R01HD104814-01A
• Status: Recruiting
• Start date: September 2014
• Est. completion date: September 2024

Study information

• Verified date: July 2023
• Source: State University of New York at Buffalo
• Contact: Thomas J. Langan, MD
• Phone: 716-888-4732
• Email: tjlangan[@]buffalo.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this study is to develop a clinical database of individuals diagnosed with Krabbe disease in order to determine which symptoms herald the onset of clinical disease in the various phenotypes of Krabbe disease; to determine whether level of GALC enzyme activity, or a specific genetic mutation predict the clinical course; and to determine which neurodiagnostic tests predict onset and/or severity of the disease.

Description:

The purported incidence of Krabbe disease is 1/250,000 live births. It is believed that 80-90% of affected children will have the early-infantile form of the disease. Other forms of the disease, however, occur throughout life. Unfortunately neither enzyme activity levels nor specific genetic mutation reliably predict phenotype. Since the only treatment for Krabbe disease is bone marrow transplantation, it is crucial to be able to identify prognostic factors, which will accurately predict the disease course. At this time the medical literature is limited regarding the clinical signs and symptoms of the later-onset forms of Krabbe disease, as well as their age of onset, and survival of these individuals.

Early-infantile Krabbe disease has a uniformly fatal outcome if untreated, and later-onset forms remain at-risk for developing symptoms. The only available treatment, pooled cord-blood transplantation, has a 10-20% mortality rate.

The vast majority of children who screen positively for Krabbe disease during newborn screening have an uncertain prognosis. No single diagnostic test available currently can accurately predict the onset of symptoms. Consequently, improved phenotypic understanding will enhance the diagnostic paradigm for Krabbe disease, and will facilitate more timely diagnosis and treatment.

The information collected in the registry will be used to improve accuracy of diagnosis, and to prevent children who are not destined to develop Krabbe from being subjected unnecessarily to treatment.

The hypotheses to be tested include:

• a detailed database will broaden phenotypic understanding of Krabbe disease;

• new therapies will result from better phenotypic understanding of this disorder.

A questionnaire will be collected at time of enrollment with information pertaining to an individual affected by Krabbe disease. Clinical information to be collected will include: age at onset of symptoms; type of symptoms; age at diagnosis; level of GALC enzyme activity; identification of the specific genetic mutation; results of any available brain MRI imaging evaluations; results of any available spinal fluid protein analyses; results of any available brainstem auditory evoked response evaluations; results of any available visual evoked response evaluations; and results of any available nerve-conduction-velocity studies. If possible, CD-ROMs containing the imaging data and physician reports of brain MRI imaging evaluations will be obtained. Potential prognostic indicators based on molecular genetic results, GALC enzyme level, detected potential biomarkers, and neurodiagnostic testing will be analyzed. Information on the status of participant's general health, disease progression, impact of the disease, neurologic symptoms, and developmental milestones will be collected through follow-up phone calls with parents or caregivers.

After de-identification, the data will be entered into the Krabbe clinical database at the University at Buffalo's Center of Excellence in Bioinformatics, and/or the Population Health Observatory on the South Campus, and/or the Longitudinal Pediatric Data Resource, a tool provided by the Newborn Screening Translational Research Network.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Anyone diagnosed with Krabbe disease

• Anyone at-risk for Krabbe disease

• Family members of someone diagnosed with, or at-risk for, Krabbe disease.

Exclusion Criteria:

• Anyone who is not diagnosed with, or at-risk for, Krabbe disease

• Anyone who is not a family member of someone diagnosed with, or at-risk for, Krabbe disease

Related Conditions & MeSH terms

• Krabbe Disease
• Leukodystrophy, Globoid Cell

Locations

Country	Name	City	State
United States	State University of New York at Buffalo	Buffalo	New York

Sponsors (5)

Lead Sponsor	Collaborator
State University of New York at Buffalo	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Lysosomal Disease Network, National Center for Advancing Translational Sciences (NCATS), Rare Diseases Clinical Research Network

Country where clinical trial is conducted

United States, 

References & Publications (2)

Carter RL, Wrabetz L, Jalal K, Orsini JJ, Barczykowski AL, Matern D, Langan TJ. Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically? J Neurosci Res. 2016 Nov;94(11):1084-93. doi: 10.1002/jnr.23793. — View Citation

Langan TJ, Barcykowski AL, Dare J, Pannullo EC, Muscarella L, Carter RL. Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease. J Neurosci Res. 2016 Nov;94(11):1189-94. doi: 10.1002/jnr.23787. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	The longevity of participants will be recorded using their date of death, or conclusion of this study, whichever occurs first.	up to 5 years

External Links

•   Eunice Kennedy Shriver National Institute of Child Health and Human Development
•   Hunter James Kelly Research Institute, University at Buffalo - home page
•   Hunter's Hope Foundation, one of the funders of this research study - their home page
•   Lysosomal Disease Network, one of the funders of this research study - their home page
•   Newborn Screening Translational Research Network - their home page
•   Rare Diseases Clinical Research Network, the funder of the Lysosomal Disease Network