Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

Recruiting

• Conditions: CLN2 Disease; CLN14 Disease; CLN1 Disease; CLN3 Disease; CLN7 Disease; CLN10 Disease; Neuronal Ceroid Lipofuscinosis; CLN6 Disease; CLN8 Disease; CLN11 Disease
• Interventions: Other: Natural History

• Registration Number: NCT04613089
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

Brief Summary

This is an observational study that aims at assessing the natural history of NCL diseases as part of the international DEM-CHILD Database.

1. Patient data are collected from medical records, patient questionnaires and routine follow up clinical examinations with focus on assessing progression in key areas of disease such as motor, language, cognition, seizures, vision, and behavior.

2. A local biorepository of samples from genetically defined NCL patients will be established as well as a virtual biorepository within the DEM-CHILD DB to be able to easily localize international availability of patient samples.

Detailed Description

NCLs (Neuronal Ceroid Lipofuscinoses) are a group of rare, inherited, neurodegenerative disorders, also known as Batten disease. Until now, 13 different genes causing different subtypes of disease are known. The genetic mutations cause a symptom complex of progressive loss of acquired skills in the domains of motor function, cognition and visual function, leading to ataxia, movement disorder, dementia, blindness and seizures. In the area of genetic testing, variable clinical phenotypes become more and more prevalent. The disease-mechanisms as well as the exact clinical course of the diseases are currently still not fully understood and documented. Although descriptions of the clinical spectrums exist, the natural history needs to be defined as accurately as possible. These data are urgently needed as clinical control data helping to test the therapeutic efficacy of emerging experimental therapies.

Since samples of genetically defined patients are rare and therefore limited for research, there is an urgent need for researchers to localize and access samples internationally. With the establishment of a local NCL-biorepository and virtual sample localization internationally, scientists worldwide may have a faster way to access needed samples for advancing research.

Any NCL patient with a confirmed molecular diagnosis can join the retrospective and prospective natural history data collection. It is also possible for families with already deceased patients to participate in the retrospective analysis part of the data collection if the genetic mutation is known.

Study Timeline

• Study Start: 2020-04-08
• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-10-27
• Study First Posted: 2020-11-03
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-22
• Last Update Posted: 2021-10-29
• Primary Completion: 2050-04-08
• Study Completion: 2050-04-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patients with a confirmed molecular diagnosis of a form of NCL Disease

Additional inclusion criteria for Group/Cohort: "CLN2 Disease - ERT (Brineura) Treated":

• Documented diagnosis of TPP1 deficiency
• Previous or current treatment with intracerebroventricular ERT with cerliponase alpha
• Patients that are currently participating in post-marketing studies will be allowed to participate.

Exclusion Criteria

• Patients with no confirmed molecular diagnosis of a form of NCL Disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CLN5 Disease	Natural History	Patients with genetic mutations in the CLN5 gene.
CLN7 Disease	Natural History	Patients with genetic mutations in the CLN7/MFSD8 gene.
CLN11 Disease	Natural History	Patients with genetic mutations in the CLN11/GRN gene.
CLN13 Disease, Kufs Disease Type B	Natural History	Patients with genetic mutations in the CLN13/CTSF gene, causing a lysosomal enzyme deficiency of Cathepsin F.
CLN14 Disease	Natural History	Patients with genetic mutations in the CLN14/KCTD7 gene.
CLN2 Disease - ERT (Brineura) treated	Natural History	Patients with genetic mutations in the CLN2/TPP1 gene, causing a lysosomal enzyme deficiency of TTP1, previously and/or currently receiving enzyme-replacement therapy (ERT) with Cerliponase alpha (Brineura).
CLN2 Disease, Jansky-Bielschowsky Disease	Natural History	Patients with genetic mutations in the CLN2/TPP1 gene, causing a lysosomal enzyme deficiency of TTP1.
CLN1 Disease, Haltia-Santavuori Disease	Natural History	Patients with genetic mutations in the CLN1/PPT1 gene, causing a lysosomal enzyme deficiency of PPT1.
CLN12 Disease	Natural History	Patients with genetic mutations in the CLN12/ATP13A2 gene.
CLN4 disease, Parry disease	Natural History	Patients with genetic mutations in the CLN4/DNAJC5 gene.
CLN6 Disease, Kufs Disease Type A	Natural History	Patients with genetic mutations in the CLN6 gene.
CLN3 Disease, Spielmeyer-Vogt-Sjögren-Batten Disease	Natural History	Patients with genetic mutations in the CLN3 gene.
CLN8 Disease	Natural History	Patients with genetic mutations in the CLN8 gene.
CLN10 Disease	Natural History	Patients with genetic mutations in the CLN10/CTSD gene, causing a lysosomal enzyme deficiency of Cathepsin D.

Primary Outcome Measures

Name	Time	Method
Identification of key symptoms of disease, natural history of disease progression and development of quantitative tools for rating disease progression that can be used as therapeutic outcome measures for emerging experimental therapies.	Up to 30 years	Evaluation of Medical history from patient interviews and medical chart review. Evaluating data from clinical routine follow up exams (e.g. brain imaging MRI, ophthalmologic assessments, OCT, EEG, cardiology assessments, cognitive assessments, developmental scales, clinical rating scales).
Establish well characterized Natural History Cohorts from genetically defined NCL patients to provide these as Natural History Control Cohorts for new experimental therapy trials.	Up to 30 years	Analysis of retrospective and prospective data from patient interviews and medical chart review as well as clinical routine follow up exams (e.g. brain imaging MRI, ophthalmologic assessments, OCT, EEG, cardiology assessments, cognitive assessments, developmental scales, clinical rating scales).

Secondary Outcome Measures

Name	Time	Method
Establish a virtual biorepository from genetically defined NCL patients within the DEM-CHILD Database.	Up to 30 years	Datacollection of available biospecimens from genetically defined NCL patients and the collecting center contacts within the DEM-CHILD DB.
Establish a biorepository of samples from genetically defined NCL patients.	Up to 30 years	- Collection of biospecimens that have been collected within treatment as part of standard of care.

Trial Locations

Locations (1)

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany