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Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis

Completed
Conditions
Batten Disease
Late Infantile Neuronal Ceroid Lipofuscinosis
Registration Number
NCT01035424
Lead Sponsor
Weill Medical College of Cornell University
Brief Summary

The primary aim of the study is to assess the genotype - phenotype correlations of the CNS manifestations of late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, rare, recessive disorder of the CNS in children. This study will be accomplished by comparing the genotype to a neurologic assessment and Weill Cornell LINCL scale, the UBDRS scale, the standardized CHQ quality of life scale, and the Mullen scale; magnetic resonance imaging (MRI); and routine clinical evaluations. This study is designed to run parallel to a separate study which is being done by the Department of Genetic Medicine, which will use gene transfer to treat the central nervous system (CNS) manifestations of late infantile neuronal ceroid lipofuscinosis.

Detailed Description

This protocol is designed to study the natural disease process of LINCL. We propose to assess the correlation between genotype (genetic constitution) and phenotype (observable characteristics) of late infantile neuronal ceroid lipofuscinosis (LINCL) in children diagnosed with LINCL in all stages. LINCL is a form of Batten disease that affects the brain of children and prevents it from functioning properly. These children are born with genetic changes called mutations that result in the inability of the brain to properly recycle proteins in the brain. The recycling failure leads to death of the nerve cells in the brain and progressive loss of brain function. Children with Batten disease are normal at birth but by age 2 to 4 have motor and vision problems which progress rapidly to death at age approximately 10 years old. There are no therapies available to treat the disease. This study is designed to run parallel to the gene transfer protocol, which will include 16 individuals in two groups: Group A will receive 9.0x10\^11 genome copies (gc) of the vector and Group B will receive 2.85x10\^11 gc; we anticipate that we will be able to capture a one-time genotype - phenotype snapshot for all n=32, and an 18 months genotype - phenotype progression assessment for n=16.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in Weill-Cornell LINCL scale at 18 monthsDay 0, 18 months

The Weill Cornell LINCL scale, a 12 point scale which combines assessment of feeding, gait, motor and language to give an overall assessment of various CNS functions

Change in MRI parameters at 18 monthsDay 0, 18 months

MRI assessment at various intervals Day 0 and month 18. Based on previous analyses, we have determined that 3 imaging parameters (% grey matter volume, % ventricular volume and cortical apparent diffusion coefficient) correlate best with age and with the Weill Cornell LINCL scale. These 3 imaging parameters will be used to assess disease progression in this screening protocol and the effect of the gene transfer in the IRB approved gene transfer trials (IRB #0810010013 and #1005011054). For those children available to continue in the study, all parameters will be re-assessed by comparing baseline evaluations to month 18 evaluation.

Secondary Outcome Measures
NameTimeMethod
Change in CHQ or ITQoLDay 0, 18 months

Quality of life questionnaires which will be completed by at least one parent/legal guardian at the time of the LINCL patients' visits to Weill Cornell16,17; we will administer either survey depending on the age of the subject independently to each parent to minimize observer bias if both parents are present.

Change in Mullen ScaleDay 0, 18 months

A pediatric developmental psychological rating scale

Trial Locations

Locations (1)

Weill Cornell Medicine

🇺🇸

New York, New York, United States

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