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Neurofilament Light- Chain in Ataxia Telangiectasia

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ClinicalTrials.gov Identifier: NCT04605523
Recruitment Status : Enrolling by invitation
First Posted : October 28, 2020
Last Update Posted : October 30, 2020
Sponsor:
Information provided by (Responsible Party):
Stefan Zielen, Johann Wolfgang Goethe University Hospital

Study Description
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Brief Summary:

Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. Currently there are no curative therapy options. The clinical presentation of the disease has a wide variety is linked to the proven mutation, immunological status and residual ATM kinase activity. Apart from these prognostic markers, hardly any biomarker to predict disease course is available. Aim of the present proposal is to evaluate serum concentrations of neurofilament - light chain in the serum of whole blood as biomarker of neurodegeneration prospectively. In addition to that, the investigators will examine the evolution of neurofilament - light chain longitudinally by blood samples from our biobank as well as the concentration of neurofilament - light chain in cerebrospinal fluid (CSF) of affected A-T patients from our biobank.

As in other neurodegenerative disorders and ataxias, the investigators expect that neurofilament- light chain levels are increased in the A-T cohort and correlated to the neurological status of A-T patients evaluated by means of AT-score.


Condition or disease Intervention/treatment
Ataxia Telangiectasia Procedure: blood withdrawal

Detailed Description:

A-T is a neurodegenerative disease with mutation in the ATM gene. The clinical presentation is complex and affects many different organ systems. Typical findings are progressive cerebellar ataxia, malnutrition, immunodeficiency, chromosomal instability and cancer susceptibility. In addition, new disease entities such as hepatopathy, diabetes and endocrinological alterations are coming to the force.

The severity of the disease is closely related to presence of residual kinase activity, immunological status and specific mutations. However, the individual course of the disease is hard to predict. There is an urgent need to find and define reliable biomarkers for disease progression in order to estimate the prognosis of individual disease course. According the classification of estimated disease severity, the most suitable therapy and support can be organized.

In many other neurodegenerative disorders neurofilament- light chain has been reported to be a sensitive and reproducable serum biomarker for disease progression, activity and monitoring of therapy efficaciousness. Neurofilament proteins indicate neuroaxonal damage independent of causal pathway, the advantage of neurofilaments as a biomarker of disease progression is that levels rise upon neuroaxonal damage not only in CSF but also in blood. Therefore, they can be used to monitor disease activity without invasive procedures.

The aim of the proposal is to measure and evaluate neurofilament-light chain as serum biomarker of disease progression in A-T patients. Additionally, the investigators will measure neurofilament-light chain in CSF from their human biobank and characterize the individual evolution in the serum of whole blood taken from the biobank.

In the prospective part of the study, the investigators will correlate the levels of neurofilament to A-T scores for neurological assessment.

Study Design
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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neurofilament Light- Chain as Biomarker for Neurodegeneration in Ataxia Telangiectasia
Actual Study Start Date : February 1, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Patients with Ataxia Telangiectasia Procedure: blood withdrawal
Additional blood sample will be taken within blood collection as part of standard care
Healthy controls Procedure: blood withdrawal
Additional blood sample will be taken within blood collection as part of standard care


Outcome Measures
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Primary Outcome Measures :
  1. Neurofilament - light chain [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Increase of neurofilament between age groups: A: 3-6 years; B: 6- <12 years ; C:12-18 years , D: >18 years. Comparison of absolute levels neurofilament (pg/ml) between groups


Secondary Outcome Measures :
  1. Absolute increase per year of neurofilament (pg/ml) [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Absolute increase per year of neurofilament (pg/ml)

  2. Correlation of neurofilament with age [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Correlation of neurofilament with age

  3. Correlation of neurofilament with A-T score [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Correlation of neurofilament with A-T score


Other Outcome Measures:
  1. Variability of levels of neurofilament within 12 months [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Variability of levels of neurofilament within 12 months

  2. Levels of neurofilament in cerebrospinal fluid (CSF) [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Levels of neurofilament in cerebrospinal fluid (CSF)

  3. Correlation of neurofilament between serum and CSF [ Time Frame: 01 Feb 2020 - 31 Dec 2020 ]
    Correlation of neurofilament between serum and CSF


Biospecimen Retention:   Samples Without DNA
Serum of whole blood CSF

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Patients with clinically / and or genetically confirmed diagnosis of ataxia telangiectasia
Criteria

Inclusion Criteria:

  • Informed consent
  • Patients: aged ≥2 and 45 years
  • known A-T

Exclusion Criteria:

  • cranial trauma in the last 6 months
  • ongoing malignant disease
  • Chronic diseases or infections (e.g. HIV, Tbc)
  • Pregnancy
  • Alcohol, substance or drug abuse
  • inability to capture extend and consequences of the study
Contacts and Locations
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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): NCT04605523


Locations
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Germany
University Children´s Hospital, Ped. Pulmonology
Frankfurt, Hessen, Germany, 60590
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
Investigators
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Principal Investigator: Stefan Zielen, Prof. Dr. University Children´s Hospital, Pediatric Pulmonology
More Information
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
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Responsible Party: Stefan Zielen, Head of Pediatric Pulmonology, Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier: NCT04605523    
Other Study ID Numbers: 168/18
First Posted: October 28, 2020    Key Record Dates
Last Update Posted: October 30, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Stefan Zielen, Johann Wolfgang Goethe University Hospital:
Ataxia telangiectasia
neurodegeneration
biomarker
 disease progression
CSF
Neurofilament light chain
Additional relevant MeSH terms:
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Ataxia
Cerebellar Ataxia
Ataxia Telangiectasia
Telangiectasis
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
 Vascular Diseases
Cardiovascular Diseases
Spinocerebellar Ataxias
Neurocutaneous Syndromes
Genetic Diseases, Inborn
Primary Immunodeficiency Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases