Investigations of Juvenile Neuronal Ceroid Lipofuscinosis

NCT ID: NCT03307304

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-11-27

Study Completion Date

2050-12-31

Brief Summary

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Background:

CLN3, or Batten disease, is a genetic disorder. This deadly disease leads to decline of brain and nervous system functions. Symptoms of CLN3 typically occur between 4 and 7 years of age. They include changes in how a person sees, thinks, and moves. CLN3 can also cause seizures. No effective treatments for the disease are yet known. There is limited testing of potential therapies. Researchers want to study CLN3 more so they can improve future therapies.

Objective:

To identify clinical or biochemical markers that can be used as therapeutic outcome measures for CLN3.

Eligibility:

People with CLN3. It must be based on

Two CLN3 mutations OR

One CLN3 mutation AND findings seen with a powerful microscope

Family members of a person with CLN3.

Design:

Participants will have already been referred to NIH for CLN3 evaluation.

If participants agree to do the study, they will:

1. give spinal fluid, blood, urine, and skin samples. They may provide other samples if they were already collected. These may include cells, surgical specimens, and DNA.
2. will be seen by multiple healthcare specialists.

Participants may provide medical records or photos. Participants will sign a release of medical records form.P

Researchers may send samples or clinical data to other investigators. For research testing, the samples will not include the participant s name. For a test in a clinical lab, researchers will include the participant s name. These results will become part of the clinical record at NIH.

Detailed Description

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Study Description:

The purpose of this protocol is to obtain both baseline and rate of progression data on clinical and biochemical markers that may later be used as an outcome measure in a clinical trial, and to establish a biorepository of samples from participants with CLN3 or CLN3-

related conditions. For comparisons, focused clinical data and relevant evaluations and biospecimens will also be collected from individuals with Neuronal Ceroids Lipofuscinosis (NCL) of other types and from family members of all affected individuals.

Objectives:

Primary Objective:

1. Identify clinical or biochemical markers that can be used as therapeutic outcome measures for CLN3-related conditions.
2. Evaluate clinical aspects of CLN3-related conditions to provide tools for future therapeutic trials.

Secondary Objectives:

Establish a biorepository of samples from well-characterized individuals with CLN3-related conditions, and family members of individuals with CLN3-related conditions, for future research related to CLN3.

Endpoints:

Primary Endpoint:

1. Blood, urine, or CSF biomarkers.
2. Proportion of participants who achieve a clinically valid and interpretable score on administered measures.
3. Scores obtained for each administered measure.

Secondary Endpoints:

Tolerability and feasibility of each measure of the clinical battery of assessments based on clinician observation.

Conditions

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Juvenile Neuronal Ceroid Lipofuscinosis (CLN3) Batten Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Family members

Unaffected family members of individuals diagnosed with CLN3-Batten

No interventions assigned to this group

Proband/Affected Individuals

Individuals diagnosed with CLN3-Batten

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

For the Main and Sub-Studies, participants \> 1 week of age, of all genders, demographics, geographic locations, and disease severity will be recruited in order to obtain cross-sectional representation of CLN3-related conditions (Main and Sub-Studies) or all NCLs (Sub-Study B). Participants in the Main study will be followed at approximately yearly intervals to obtain longitudinal data. Participants in Sub-Study A may elect to send in medical records and samples only, or to come to the NIH for evaluations as outlined in Section 4. We anticipate that

participants in Sub-Study B will be seen mostly at NCL/CLN3-related family conferences.

Main Study:

Individuals \> 1 week of age with a diagnosis of CLN3 or a CLN3-related/other NCL-type condition. Diagnosis determined by one of the following:

1. Two CLN3 or NCL condition-appropriate genetic mutations
2. One CLN3 mutation AND

i) clinical presentation suggestive of CLN3, OR

ii) characteristic electron microscopy (EM) findings (such as curvilinear body, fingerprint profile, granular osmiophilic deposits).

Sub-Study A:

Individuals \> 1 week of age with a diagnosis of CLN3 or CLN3-related/other NCL-type condition. Diagnosis determined by one of the following:

1. Two CLN3 or condition-appropriate genetic mutations
2. One CLN3 mutation AND

i) clinical presentation suggestive of CLN3, OR

ii) characteristic electron microscopy (EM) findings (such as curvilinear body, fingerprint profile, granular osmiophilic deposits).

OR

Individuals \> 1 month of age who have family member(s) diagnosed with CLN3 or CLN3-related/other NCL-type condition.

Sub-Study B:

Individuals \> 1 week of age with a clinical diagnosis of CLN3 or NCL.

OR

Individuals \> 1 month of age who have family member(s) diagnosed with CLN3 or NCL.

Exclusion Criteria

Main Study:

1. Individuals who cannot travel to the NIH because of their medical condition.
2. Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.
3. Females who are pregnant.

Sub-Studies A and B:

1. Unaffected individuals \> 18 years of age who have cognitive impairments.
2. Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.
Minimum Eligible Age

1 Week

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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An N Dang Do, M.D.

Role: PRINCIPAL_INVESTIGATOR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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An N Dang Do, M.D.

Role: CONTACT

(301) 496-8849

Facility Contacts

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For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

800-411-1222 ext. TTY8664111010

References

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Luckett A, Yousef M, Tifft C, Jenkins K, Smith A, Munoz A, Quimby R, Porter FD, Dang Do AN. Anesthesia outcomes in lysosomal disorders: CLN3 and GM1 gangliosidosis. Am J Med Genet A. 2023 Mar;191(3):711-717. doi: 10.1002/ajmg.a.63064. Epub 2022 Dec 2.

Reference Type DERIVED
PMID: 36461157 (View on PubMed)

Dang Do AN, Thurm AE, Farmer CA, Soldatos AG, Chlebowski CE, O'Reilly JK, Porter FD. Use of the Vineland-3, a measure of adaptive functioning, in CLN3. Am J Med Genet A. 2022 Apr;188(4):1056-1064. doi: 10.1002/ajmg.a.62607. Epub 2021 Dec 16.

Reference Type DERIVED
PMID: 34913584 (View on PubMed)

Abdennadher M, Inati S, Soldatos A, Norato G, Baker EH, Thurm A, Bartolini L, Masvekar R, Theodore W, Bielekova B, Porter FD, Dang Do AN. Seizure phenotype in CLN3 disease and its relation to other neurologic outcome measures. J Inherit Metab Dis. 2021 Jul;44(4):1013-1020. doi: 10.1002/jimd.12366. Epub 2021 Feb 15.

Reference Type DERIVED
PMID: 33550636 (View on PubMed)

Related Links

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Other Identifiers

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18-CH-0002

Identifier Type: -

Identifier Source: secondary_id

180002

Identifier Type: -

Identifier Source: org_study_id

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