Neurofilament Light- Chain in Ataxia Telangiectasia

Neurofilament Light- Chain as Biomarker for Neurodegeneration in Ataxia Telangiectasia

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.

Study Overview

• Status: Unknown
• Conditions: Ataxia Telangiectasia
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • University Children´s Hospital, Ped. Pulmonology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 41 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with clinically / and or genetically confirmed diagnosis of ataxia telangiectasia

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurofilament - light chain	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	01 Feb 2020 - 31 Dec 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute increase per year of neurofilament (pg/ml)	Absolute increase per year of neurofilament (pg/ml)	01 Feb 2020 - 31 Dec 2020
Correlation of neurofilament with age	Correlation of neurofilament with age	01 Feb 2020 - 31 Dec 2020
Correlation of neurofilament with A-T score	Correlation of neurofilament with A-T score	01 Feb 2020 - 31 Dec 2020

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability of levels of neurofilament within 12 months	Variability of levels of neurofilament within 12 months	01 Feb 2020 - 31 Dec 2020
Levels of neurofilament in cerebrospinal fluid (CSF)	Levels of neurofilament in cerebrospinal fluid (CSF)	01 Feb 2020 - 31 Dec 2020
Correlation of neurofilament between serum and CSF	Correlation of neurofilament between serum and CSF	01 Feb 2020 - 31 Dec 2020

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Investigators: Principal Investigator: Stefan Zielen, Prof. Dr., University Children´s Hospital, Pediatric Pulmonology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: biomarker; neurodegeneration; Neurofilament light chain; disease progression; CSF; Ataxia telangiectasia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Dyskinesias; DNA Repair-Deficiency Disorders; Neurocutaneous Syndromes; Cerebellar Diseases; Primary Immunodeficiency Diseases; Spinocerebellar Ataxias; Ataxia; Telangiectasis; Cerebellar Ataxia; Ataxia Telangiectasia
• Other Study ID Numbers: 168/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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