Genotype - Phenotype Correlations of LINCL

July 28, 2016 updated by: Weill Medical College of Cornell University

Genotype - Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis

In a separate protocol the Department of Genetic Medicine is proposing to carry out a study using gene transfer to treat the central nervous system (CNS) manifestations of late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, rare, recessive disorder of the (CNS) in children. In the context that there is little known about the genotype - phenotype correlations of LINCL, and that our referral far exceed the number (n=11) of children that will be entered into the gene transfer protocol, we are proposing to capitalize on this unique opportunity to evaluate this disorder in this separate study. In this context, the aim of this protocol is to study the genotype - phenotype correlations of the CNS manifestations of late infantile neuronal ceroid lipofuscinosis. This will be accomplished by comparing the genotype to a neurologic assessment, and LINCL clinical rating scale; magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) assessments of the CNS; and routine clinical evaluations.

Study Overview

Status

Completed

Conditions

Detailed Description

This proposed clinical protocol is designed to assess genotype - phenotype correlations of LINCL, including a preliminary assessment regarding the genotype - phenotype correlations of progressive CNS deterioration inherent to this disorder. The trial will include the primary endpoint of neurological assessment including the LINCL clinical rating scale and parental evaluations; and the secondary endpoint of magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) assessments of the CNS.

The study will be carried out in children diagnosed with LINCL in all stages. The staging is based on a modification of the scale of Steinfeld et al (Steinfeld, 2002). The study anticipates a total n=30 children assessed over a period of 18 months. Of these, we anticipate that approximately two-thirds will not be entered into the proposed gene therapy protocol and thus approximately n=20 will be available for this study to be reassessed at 1 year. Thus, we anticipate that we will be able to capture a one-time genotype - phenotype snapshot for all n=30, and a 1 year genotype - phenotype progression assessment for n=20.

Study Type

Observational

Enrollment (Actual)

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

2 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study will be carried out in children diagnosed with LINCL in all stages.

Description

Inclusion Criteria:

A definitive diagnosis of late infantile neuronal ceroid lipofuscinosis
Between the age of 2 and 18 years
Not previously participated in a gene transfer study for LINCL.
Parents of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments.
Both parents or legal guardians must give consent for their child's participation in the research study.

Exclusion Criteria:

Individuals with heart disease that would be a risk for anesthesia.
Concurrent participation in any other FDA approved Investigational New Drug clinical protocol is not allowed, although the Principal Investigator will work with other doctors to accommodate specific requests (e.g., a study of nutritional supplements probably would not be a disqualification).
Individuals who have a contraindication to MRI/MRS assessment including: (1) heart pacemaker and/or related implants; (2) metal fragment/chip in the eye or other sites; (3) an aneurysm clip in their brain; and (4) metallic inner ear implants.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation analysis between genotype (genetic constitution) and baseline Time Frame: 18 months	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation analysis between genotype and rate of CNS decline Time Frame: 18 months	18 months

Collaborators and Investigators

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

Sponsor

Weill Medical College of Cornell University

Collaborators

Nathan's Battle Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2004

Primary Completion (ACTUAL)

September 1, 2009

Study Completion (ACTUAL)

September 1, 2009

Study Registration Dates

First Submitted

September 6, 2005

First Submitted That Met QC Criteria