Clinical trial NCT01035424: Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis
Official title: Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Batten Disease
Late Infantile Neuronal Ceroid Lipofuscinosis
Keywords: Batten Disease
Late Infantile Neuronal Lipofuscinosis
LINCL
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institutes of Health (NIH)
First posted: 2009-12-18
Enrollment: 48
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be carried out in children diagnosed with LINCL in all stages.

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.

Eligibility criteria: Inclusion Criteria.

1. Definitive diagnosis of LINCL, based on clinical phenotype and genotype.
2. The subject must be between the age of 2 and 18 years.
3. The subject will not previously have participated in a gene transfer or stem cell study.
4. 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, and both parents or legal guardians must give consent for their child's participation.

Exclusion criteria.

1. Presence of other significant medical or neurological conditions may disqualify the subject from participation in this study e.g.,malignancy, congenital heart disease, liver or renal failure.
2. Subjects without adequate control of seizures.
3. Subjects with heart disease that would be a risk for anesthesia or a history of major risk factors for hemorrhage.
4. Subjects who cannot participate in MRI studies.
5. Concurrent participation in any other FDA approved Investigational New Drug.
6. Subjects with history of prolonged bleeding or abnormal platelet function or taking aspirin.

Primary outcomes:
measure: Change in Weill-Cornell LINCL scale at 18 months
timeFrame: Day 0, 18 months
measure: Change in MRI parameters at 18 months
timeFrame: Day 0, 18 months
Secondary outcomes:
measure: Change in CHQ or ITQoL
timeFrame: Day 0, 18 months
measure: Change in Mullen Scale
timeFrame: Day 0, 18 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Ronald G. Crystal, MD
role: PRINCIPAL_INVESTIGATOR
References: