Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

Active, not recruiting

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

• Registration Number: NCT04098211
• Lead Sponsor: Children's Hospital of Orange County

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.

Detailed Description

This study aims characterize the natural history of atypical TPP1 deficiency patients via longitudinal multidisciplinary assessments.

Multifaceted clinical, laboratory, imaging, and diagnostic assessments will be performed at regular intervals upon enrolled aTPP1 deficiency patients, collated, and analyzed over a three-year longitudinal period.

Study Timeline

• Study First Submitted: 2019-07-22
• Study First Submitted QC: 2019-09-18
• Study First Posted: 2019-09-23
• Study Start: 2019-11-01
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-15
• Last Update Posted: 2024-02-20
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Electroretinogram (ERG)	At baseline and every 6 months afterwards, up to 3 years	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.
CLN2 Disease Severity Scoring	At baseline and every 3 months afterwards, up to 3 years	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).
Optical Coherence Tomography (OCT)	At baseline and every 6 months afterwards, up to 3 years	OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses.
Gait Assessment	At baseline and every 6 months afterwards, up to 3 years	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.
Brain Magnetic Resonance Imaging (MRI)	At baseline and every 12 months afterwards, up to 3 years	Pre/post-contrast images will be acquired to perform volumetric studies and white matter assessment.
Electroencephalography (EEG)	At baseline and every 12 months afterwards, up to 3 years	Photoparoxysmal response: present/absent
Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV)	At baseline and every 12 months afterwards, up to 3 years	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).
CSF Testing	At baseline and every 3 months afterwards, up to 3 years	Standard laboratory testing and biobanking / storage of remaining CSF (via Ommaya if on enzyme replacement; via lumbar puncture if not on enzyme replacement)

Trial Locations

Locations (1)

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States