Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency (Neuronal Ceroid Lipofuscinosis Type 2) Patients

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuronal Ceroid-Lipofuscinoses; Neuronal Ceroid Lipofuscinosis CLN2; Spinocerebellar Ataxia, Autosomal Recessive 7

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 Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Children's Hospital of Orange County

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Natural History; Neuronal Ceroid Lipofuscinosis; Atypical CLN2 Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Neuronal Ceroid-Lipofuscinoses
• Other Study ID Numbers: 190219

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No