Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

NCT04098211 | Active Not Recruiting

• 1 other identifier: 190219
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to gather information on the possible symptoms that patients with atypical neuronal ceroid lipofuscinosis type 2 (also known as aTPP1 or atypical tripeptidyl peptidase deficiency) have and how they change over time.

Conditions

Neuronal Ceroid-Lipofuscinoses; Neuronal Ceroid Lipofuscinosis CLN2; Spinocerebellar Ataxia, Autosomal Recessive 7

Keywords

Neuronal Ceroid Lipofuscinosis; Atypical CLN2 Disease; Natural History

Outcome Measures

Primary Outcomes (11)

• CLN2 Disease Severity Scoring

  Modified Hamburg Rating Scale. The rating scale consists of two domains (motor function, language). Within each domain, a score from 0 to 3 is assigned and overall scores are calculated by summing the domain scores for final rating of 0 (severely impaired) to 6 (normal).

  At baseline and every 3 months afterwards, up to 3 years

• Electroretinogram (ERG)

  Standard ERG will be performed to measure function of cones and rods of the inner and outer photoreceptor layers which amplitudes are typically decreased in classical TPP1 deficiency.

  At baseline and every 6 months afterwards, up to 3 years

• Optical Coherence Tomography (OCT)

  OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses.

  At baseline and every 6 months afterwards, up to 3 years

• Gait Assessment

  Gait assessment is acquired utilizing infrared sensors applied to participant's clothing and will include collection of walking speed, cadence, swing phase, stride length and time, walking base width, stance phase, and double limb support phase.

  At baseline and every 6 months afterwards, up to 3 years

• Brain Magnetic Resonance Imaging (MRI)

  Pre/post-contrast images will be acquired to perform volumetric studies and white matter assessment.

  At baseline and every 12 months afterwards, up to 3 years

• Electroencephalography (EEG)

  EEG will be obtained and analyzed for changes that may be distinctive for TPP1 deficiency. Evaluation of background activity, mild/moderate/severe slowing for age.

  At baseline and every 12 months afterwards, up to 3 years

• Electroencephalography (EEG)

  EEG will be obtained and analyzed for changes that may be distinctive for TPP1 deficiency. Interictal discharges: location, focal/generalized, discharge burden.

  At baseline and every 12 months afterwards, up to 3 years

• Electroencephalography (EEG)

  Seizures.

  At baseline and every 12 months afterwards, up to 3 years

• Electroencephalography (EEG)

  Photoparoxysmal response: present/absent

  At baseline and every 12 months afterwards, up to 3 years

• Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV)

  WISC-IV will generate a full scale of intelligence quotient and five primary index scores: Verbal Comprehension, Visual Spatial, Fluid Reasoning, Working Memory, and Processing Speed. The WAIS-IV is scored by summing the raw scores for each subtest; each raw subtest score is then converted to a scaled scored. They are then combined to create a Full Scale IQ Index score. Test takers will also be given a score on the General Ability Index (GAI).

  At baseline and every 12 months afterwards, up to 3 years

• CSF Testing

  Standard laboratory testing and biobanking / storage of remaining CSF (via Ommaya if on enzyme replacement; via lumbar puncture if not on enzyme replacement)

  At baseline and every 3 months afterwards, up to 3 years

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any patient with documented TPP1 enzymatic deficiency or TPP1 sequence variants with onset of first symptom after 4 years of age

You may qualify if:

• Any patient with documented TPP1 enzymatic deficiency or TPP1 sequence variants
• Onset of first symptom after 4 years of age
• Parental provision of informed consent; child provision of assent (if necessary)

You may not qualify if:

• Any patient with "Classical" TPP1 deficiency (onset of first symptom prior to 4 years of age)
• Investigator assessment that patient is not suitable candidate to participate in the study

Sponsors & Collaborators

• Children's Hospital of Orange County: lead

Study Sites (1)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses; Spinocerebellar Ataxia, Autosomal Recessive 7

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: September 23, 2019
• Study Start: November 1, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-03

Locations

US (1)