Natural History of Neuronal Ceroid Lipofuscinosis, Batten's CLN6 Diseae (Batten'sCLN6)

• ClinicalTrials.gov Identifier: NCT03285425
• Recruitment Status: Recruiting
• First Posted: September 18, 2017
• Last Update Posted: November 22, 2019
• Sponsor: Emily de los Reyes
• Information provided by (Responsible Party): Emily de los Reyes, Nationwide Children's Hospital

Study Description

Brief Summary:

CLN6 is a rare, neurodegenerative disease that causes progressive loss of acquired skills with motor delay, visual loss, seizures and ataxia. The investigators propose a natural history study of this rare disorder since it is currently unknown. It is important to understand disease progression in CLN6 disease to be able to judge therapeutic efficacy as emerging therapies like gene therapy become available.

Condition or disease	Intervention/treatment
Batten Disease; CLN6	Other: Natural history

Detailed Description:

Neuronal Ceroid Lipofuscinosis (NCL) is the most common childhood neurodegenerative disorder characterized by accumulation of autofluorescent waxy lipopigments in the brain and other tissues. The symptoms manifest as blindness, seizures, ataxia, myoclonus and loss of milestones or dementia. This group of disorders caused by an intracellular accumulation of lipopigment (ceroid lipofuscin) material leads to neuronal death and is the most prevalent class of childhood neurodegenerative disease.

There are 14 types of NCL with 13 genotypes. Most of these are autosomal recessive. Neuronal ceroid lipofuscinosis, type 6 usually present like a late infantile NCL (CLN2) but can also present at as a juvenile onset (Mole). The natural history is not well established and the presentation maybe variable. There are currently no published data on the disease progression of children with CLN6 disease

CLN6 is a rare, neurodegenerative disease that causes progressive loss of acquired skills with motor delay, visual loss, seizures and ataxia. The investigators propose a natural history study of this rare disorder since it is currently unknown. Although there are descriptions of the clinical spectrum, the natural history has not been well described. It is important to understand disease progression in CLN6 disease to be able to judge therapeutic efficacy for as emerging therapies like gene therapy become available. The investigators will identify children with a genotypic diagnosis of CLN6 who are consulting Nationwide Children's hospital. The investigators will also recruit patients through family conferences of Batten's disease Support and Research association. The investigators propose a retro prospective chart review and longitudinal phone follow-up of with diagnosis of CLN6 to understand the onset and progression of this disease.

CLN6 is a rare, neurodegenerative disease that causes progressive loss of acquired skills with motor delay, visual loss, seizures and ataxia. The investigators propose a natural history study of this rare disorder since it is currently unknown. Although there are descriptions of the clinical spectrum, the natural history has not been well described. It is important to understand disease progression in CLN6 disease to be able to judge therapeutic efficacy for as emerging therapies like gene therapy become available. The investigators will identify children with a genotypic diagnosis of CLN6 who are consulting Nationwide Children's hospital. Patients will also be recruited through family conferences of Batten's disease Support and Research association.

OBJECTIVES:

The primary objectives of this study include the following:

1. Assess the natural history of CLN6 by performing a prospective, longitudinal chart review and phone follow-up of patients who have a diagnosis of Batten's disease, with a specific genotype of CLN6.
2. To promote better understanding of this disease to compare therapeutic efficacy with emerging therapies

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Natural History Study of Batten's CLN6 Disease
• Study Start Date: January 2017
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: January 2022

Groups and Cohorts

Intervention Details:

• Other: Natural history
  Parent interview

Outcome Measures

Primary Outcome Measures :

1. Natural history of disease progression [ Time Frame: Three years ]
   The investigators will assess historical data for the onset of seizures, blindness, dementia, and loss of motor skills; and will request any available MRIs and EEGs.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Study population will consist of children or adolescents (minors).

Criteria

Inclusion Criteria:

• Confirmed diagnosis of genotypic diagnosis of CLN6

Exclusion Criteria:

• Patients who do not have a genotypic diagnosis of CLN6

Contacts and Locations

Contacts

Contact: Ashley M. Falke, BHS; (614) 722-4644; ashley.falke@nationwidechildrens.org

Locations

United States, Ohio

Nationwide Children's Hospital; Recruiting

Columbus, Ohio, United States, 43205

Contact: Emily C de los Reyes, MD

Contact: Ashley Falke 614-722-4625 ext 24644

Sponsors and Collaborators

Emily de los Reyes

More Information

Publications:

Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases - clinical perspectives. Biochim Biophys Acta. 2013 Nov;1832(11):1801-6. doi: 10.1016/j.bbadis.2013.04.008. Epub 2013 Apr 17.

Canafoglia L, Gilioli I, Invernizzi F, Sofia V, Fugnanesi V, Morbin M, Chiapparini L, Granata T, Binelli S, Scaioli V, Garavaglia B, Nardocci N, Berkovic SF, Franceschetti S. Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations. Neurology. 2015 Jul 28;85(4):316-24. doi: 10.1212/WNL.0000000000001784. Epub 2015 Jun 26.

Sharp JD, Wheeler RB, Parker KA, Gardiner RM, Williams RE, Mole SE. Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis. Hum Mutat. 2003 Jul;22(1):35-42.

Gao H, Boustany RM, Espinola JA, Cotman SL, Srinidhi L, Antonellis KA, Gillis T, Qin X, Liu S, Donahue LR, Bronson RT, Faust JR, Stout D, Haines JL, Lerner TJ, MacDonald ME. Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. Am J Hum Genet. 2002 Feb;70(2):324-35. Epub 2001 Dec 21.

• Responsible Party: Emily de los Reyes, Principal Investigator, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT03285425
• Other Study ID Numbers: IRB16-00554
• First Posted: September 18, 2017
• Last Update Posted: November 22, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Emily de los Reyes, Nationwide Children's Hospital:

Batten's disease; Neuronal Ceroid Lipofuscinosis

Additional relevant MeSH terms:

Neuronal Ceroid-Lipofuscinoses; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases