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

NCT04613089 | Recruiting

• 1 other identifier: DEM-CHILD2020
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Neuronal Ceroid Lipofuscinosis; Batten Disease; CLN1 Disease; CLN2 Disease; CLN3 Disease; CLN4 Disease; CLN5 Disease; CLN6 Disease; CLN7 Disease; CLN8 Disease; CLN10 Disease; CLN11 Disease; CLN12 Disease; CLN13 Disease; CLN14 Disease

Keywords

INCL; LINCL; VLINCL; JNCL; ANCL; NCL; CLN; Batten; Childhood Dementia; Lysosomal Storage Diseases; Neurodegenerative Diseases; Neurodegenerative Disorders; Metabolic Disorders; PME; EPMR; SCAR7; SGSH; PPT1; Haltia-Santavuori Disease; TPP1; Jansky-Bielschowsky Disease; Spielmeyer-Vogt-Sjögren-Batten Disease; DNAJC5; Parry Disease; Kufs Disease Type A; MFSD8; CTSD; GRN; ATP13A2; Kufor-Rakeb Syndrome; CTSF; Kufs Disease Type B; KCTD7

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Up to 30 years

• Establish well characterized Natural History Cohorts from genetically defined NCL patients to provide these as Natural History Control Cohorts for new experimental therapy trials.

  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).

  Up to 30 years

Secondary Outcomes (2)

• Establish a biorepository of samples from genetically defined NCL patients.

  Up to 30 years

• Establish a virtual biorepository from genetically defined NCL patients within the DEM-CHILD Database.

  Up to 30 years

Study Arms (14)

CLN1 Disease, Haltia-Santavuori Disease

Patients with genetic mutations in the CLN1/PPT1 gene, causing a lysosomal enzyme deficiency of PPT1.

Other: Natural History

CLN2 Disease, Jansky-Bielschowsky Disease

Patients with genetic mutations in the CLN2/TPP1 gene, causing a lysosomal enzyme deficiency of TTP1.

Other: Natural History

CLN2 Disease - ERT (Brineura) treated

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).

Other: Natural History

CLN3 Disease, Spielmeyer-Vogt-Sjögren-Batten Disease

Patients with genetic mutations in the CLN3 gene.

Other: Natural History

CLN4 disease, Parry disease

Patients with genetic mutations in the CLN4/DNAJC5 gene.

Other: Natural History

CLN5 Disease

Patients with genetic mutations in the CLN5 gene.

Other: Natural History

CLN6 Disease, Kufs Disease Type A

Patients with genetic mutations in the CLN6 gene.

Other: Natural History

CLN7 Disease

Patients with genetic mutations in the CLN7/MFSD8 gene.

Other: Natural History

CLN8 Disease

Patients with genetic mutations in the CLN8 gene.

Other: Natural History

CLN10 Disease

Patients with genetic mutations in the CLN10/CTSD gene, causing a lysosomal enzyme deficiency of Cathepsin D.

Other: Natural History

CLN11 Disease

Patients with genetic mutations in the CLN11/GRN gene.

Other: Natural History

CLN12 Disease

Patients with genetic mutations in the CLN12/ATP13A2 gene.

Other: Natural History

CLN13 Disease, Kufs Disease Type B

Patients with genetic mutations in the CLN13/CTSF gene, causing a lysosomal enzyme deficiency of Cathepsin F.

Other: Natural History

CLN14 Disease

Patients with genetic mutations in the CLN14/KCTD7 gene.

Other: Natural History

Interventions

Natural History OTHER

Natural History and Clinical Follow Up.

CLN1 Disease, Haltia-Santavuori Disease; CLN10 Disease; CLN11 Disease; CLN12 Disease; CLN13 Disease, Kufs Disease Type B; CLN14 Disease; CLN2 Disease - ERT (Brineura) treated; CLN2 Disease, Jansky-Bielschowsky Disease; CLN3 Disease, Spielmeyer-Vogt-Sjögren-Batten Disease; CLN4 disease, Parry disease; CLN5 Disease; CLN6 Disease, Kufs Disease Type A; CLN7 Disease; CLN8 Disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Children, Adolescents, Adults

You may qualify if:

• \- Patients with a confirmed molecular diagnosis of a form of NCL Disease
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Related Publications (18)

• Rietdorf K, Coode EE, Schulz A, Wibbeler E, Bootman MD, Ostergaard JR. Cardiac pathology in neuronal ceroid lipofuscinoses (NCL): More than a mere co-morbidity. Biochim Biophys Acta Mol Basis Dis. 2020 Sep 1;1866(9):165643. doi: 10.1016/j.bbadis.2019.165643. Epub 2019 Dec 19.

  PMID: 31863828 BACKGROUND

• Nickel M, Simonati A, Jacoby D, Lezius S, Kilian D, Van de Graaf B, Pagovich OE, Kosofsky B, Yohay K, Downs M, Slasor P, Ajayi T, Crystal RG, Kohlschutter A, Sondhi D, Schulz A. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Lancet Child Adolesc Health. 2018 Aug;2(8):582-590. doi: 10.1016/S2352-4642(18)30179-2. Epub 2018 Jul 2.

  PMID: 30119717 BACKGROUND

• Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschutter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24.

  PMID: 29688815 BACKGROUND

• Gardner E, Bailey M, Schulz A, Aristorena M, Miller N, Mole SE. Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. Hum Mutat. 2019 Nov;40(11):1924-1938. doi: 10.1002/humu.23860. Epub 2019 Jul 26.

  PMID: 31283065 BACKGROUND

• Fietz M, AlSayed M, Burke D, Cohen-Pfeffer J, Cooper JD, Dvorakova L, Giugliani R, Izzo E, Jahnova H, Lukacs Z, Mole SE, Noher de Halac I, Pearce DA, Poupetova H, Schulz A, Specchio N, Xin W, Miller N. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016 Sep;119(1-2):160-7. doi: 10.1016/j.ymgme.2016.07.011. Epub 2016 Jul 25.

  PMID: 27553878 BACKGROUND

• Simonati A, Williams RE, Nardocci N, Laine M, Battini R, Schulz A, Garavaglia B, Moro F, Pezzini F, Santorelli FM. Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5. Dev Med Child Neurol. 2017 Aug;59(8):815-821. doi: 10.1111/dmcn.13473. Epub 2017 May 25.

  PMID: 28542837 BACKGROUND

• Lebrun AH, Storch S, Ruschendorf F, Schmiedt ML, Kyttala A, Mole SE, Kitzmuller C, Saar K, Mewasingh LD, Boda V, Kohlschutter A, Ullrich K, Braulke T, Schulz A. Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibship. Hum Mutat. 2009 May;30(5):E651-61. doi: 10.1002/humu.21010.

  PMID: 19309691 BACKGROUND

• Williams RE, Adams HR, Blohm M, Cohen-Pfeffer JL, de Los Reyes E, Denecke J, Drago K, Fairhurst C, Frazier M, Guelbert N, Kiss S, Kofler A, Lawson JA, Lehwald L, Leung MA, Mikhaylova S, Mink JW, Nickel M, Shediac R, Sims K, Specchio N, Topcu M, von Lobbecke I, West A, Zernikow B, Schulz A. Management Strategies for CLN2 Disease. Pediatr Neurol. 2017 Apr;69:102-112. doi: 10.1016/j.pediatrneurol.2017.01.034. Epub 2017 Feb 4.

  PMID: 28335910 BACKGROUND

• Kohlschutter A, Schulz A, Bartsch U, Storch S. Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses. CNS Drugs. 2019 Apr;33(4):315-325. doi: 10.1007/s40263-019-00620-8.

  PMID: 30877620 BACKGROUND

• Lobel U, Sedlacik J, Nickel M, Lezius S, Fiehler J, Nestrasil I, Kohlschutter A, Schulz A. Volumetric Description of Brain Atrophy in Neuronal Ceroid Lipofuscinosis 2: Supratentorial Gray Matter Shows Uniform Disease Progression. AJNR Am J Neuroradiol. 2016 Oct;37(10):1938-1943. doi: 10.3174/ajnr.A4816. Epub 2016 May 26.

  PMID: 27231226 BACKGROUND

• Dulz S, Wagenfeld L, Nickel M, Richard G, Schwartz R, Bartsch U, Kohlschutter A, Schulz A. Novel morphological macular findings in juvenile CLN3 disease. Br J Ophthalmol. 2016 Jun;100(6):824-8. doi: 10.1136/bjophthalmol-2015-307320. Epub 2015 Oct 20.

  PMID: 26486417 BACKGROUND

• Dulz S, Atiskova Y, Wibbeler E, Wildner J, Wagenfeld L, Schwering C, Nickel M, Bartsch U, Spitzer MS, Schulz A. An Ophthalmic Rating Scale to Assess Ocular Involvement in Juvenile CLN3 Disease. Am J Ophthalmol. 2020 Dec;220:64-71. doi: 10.1016/j.ajo.2020.07.015. Epub 2020 Jul 21.

  PMID: 32707205 BACKGROUND

• Mole SE, Anderson G, Band HA, Berkovic SF, Cooper JD, Kleine Holthaus SM, McKay TR, Medina DL, Rahim AA, Schulz A, Smith AJ. Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis. Lancet Neurol. 2019 Jan;18(1):107-116. doi: 10.1016/S1474-4422(18)30368-5. Epub 2018 Nov 21.

  PMID: 30470609 BACKGROUND

• Bergholz R, Kohlschutter A, Schulz A, Hubert W, Ruther K. Phenotyping heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with CLN3 mutations. Graefes Arch Clin Exp Ophthalmol. 2015 Aug;253(8):1245-50. doi: 10.1007/s00417-014-2814-0. Epub 2014 Oct 22.

  PMID: 25338278 BACKGROUND

• Schulz A, Kohlschutter 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.

  PMID: 23602993 BACKGROUND

• Paniagua Bravo A, Forkert ND, Schulz A, Lobel U, Fiehler J, Ding X, Sedlacik J, Rosenkranz M, Goebell E. Quantitative t2 measurements in juvenile and late infantile neuronal ceroid lipofuscinosis. Clin Neuroradiol. 2013 Sep;23(3):189-96. doi: 10.1007/s00062-012-0189-3. Epub 2012 Dec 23.

  PMID: 23263384 BACKGROUND

• Kousi M, Anttila V, Schulz A, Calafato S, Jakkula E, Riesch E, Myllykangas L, Kalimo H, Topcu M, Gokben S, Alehan F, Lemke JR, Alber M, Palotie A, Kopra O, Lehesjoki AE. Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. J Med Genet. 2012 Jun;49(6):391-9. doi: 10.1136/jmedgenet-2012-100859.

  PMID: 22693283 BACKGROUND

• Dulz S, Schwering C, Wildner J, Spartalis C, Schuettauf F, Bartsch U, Wibbeler E, Nickel M, Spitzer MS, Atiskova Y, Schulz A. Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease). Br J Ophthalmol. 2023 Oct;107(10):1478-1483. doi: 10.1136/bjo-2022-321260. Epub 2022 Jun 30.

  PMID: 35772852 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

All available Biomaterials from diagnostic approach and routine clinical care are collected (e.g. blood, urine, skin cells, CSF, other..).

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses; Ceroid lipofuscinosis, neuronal 5; Lysosomal Storage Diseases; Neurodegenerative Diseases; Metabolic Diseases; Kufor-Rakeb syndrome

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases

Study Officials

• Angela Schulz, MD, PhD

  Head of NCL-Specialty Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miriam Nickel, MD

CONTACT

+4940741020440; m.nickel@uke.de

Angela Schulz, MD, PhD

CONTACT

+4940741020440; anschulz@uke.de

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 30 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Head of NCL Specialty Clinic

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: November 3, 2020
• Study Start: April 8, 2020
• Primary Completion (Estimated): April 8, 2050
• Study Completion (Estimated): April 8, 2050
• Last Updated: October 29, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Access Criteria: Upon written formal request. Project description of anticipated data usage needed. Specifications for exact data access (type of NCL, retrospective or prospective data, data items) and data transfer (one-time transfer, longitudinal access) must be declared. Data transfer agreements detailing the above will need to be in place with the respective data-entering center who has full data ownership.

Locations

DE (1)