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Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04098211
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease
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.

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Study Type : Observational
Estimated Enrollment : 5 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency (Neuronal Ceroid Lipofuscinosis Type 2) Patients
Actual Study Start Date : November 1, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : December 2022





Primary Outcome Measures :
  1. CLN2 Disease Severity Scoring [ Time Frame: 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).

  2. Electroretinogram (ERG) [ Time Frame: 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.

  3. Optical Coherence Tomography (OCT) [ Time Frame: At baseline and every 6 months afterwards, up to 3 years ]
    OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses.

  4. Gait Assessment [ Time Frame: 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.

  5. Brain Magnetic Resonance Imaging (MRI) [ Time Frame: 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.

  6. Electroencephalography (EEG) [ Time Frame: At baseline and every 12 months afterwards, up to 3 years ]
    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.

  7. Electroencephalography (EEG) [ Time Frame: At baseline and every 12 months afterwards, up to 3 years ]
    EEG will be obtained and analyzed for changes that may be distinctive for TPP1 deficiency. Interictal discharges: location, focal/generalized, discharge burden.

  8. Electroencephalography (EEG) [ Time Frame: At baseline and every 12 months afterwards, up to 3 years ]
    Seizures.

  9. Electroencephalography (EEG) [ Time Frame: At baseline and every 12 months afterwards, up to 3 years ]
    Photoparoxysmal response: present/absent

  10. Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV) [ Time Frame: 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).

  11. CSF Testing [ Time Frame: 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)



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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04098211


Contacts
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Contact: Raymond Wang, MD 7145093344 rawang@choc.org

Locations
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United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Eric Rodriguez, BSc    714-509-3344    eric.rodriguez@choc.org   
Contact: Nina Movsesyan, PhD    714-509-3008    nmovsesyan@choc.org   
Principal Investigator: Raymond Wang, MD         
Sponsors and Collaborators
Children’s Hospital of Orange County
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Responsible Party: Children’s Hospital of Orange County
ClinicalTrials.gov Identifier: NCT04098211    
Other Study ID Numbers: 190219
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Children’s Hospital of Orange County:
Neuronal Ceroid Lipofuscinosis
Atypical CLN2 Disease
Natural History
Additional relevant MeSH terms:
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Spinocerebellar Ataxias
Spinocerebellar Degenerations
Neuronal Ceroid-Lipofuscinoses
Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Cerebellar Ataxia
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases