NCT02285348

Brief Summary

Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. The underlying mechanism and process of neurodegeneration leading to loss of cerebellar neurons and neurological function is largely unknown. Laboratory diagnostic approaches to neurodegeneration in A-T are hampered by sampling issues. It is dangerous, impractical, and not ethically to directly sample brain tissue by surgical biopsy. In contrast cerebrospinal fluid (CSF), a fluid that is in direct contact with brain tissue, is relatively easy to sample in a safe procedure (lumbar puncture). The aim of the proposal is to investigate oxidative stress, low grade inflammation and tissue break down in the brain of A-T patients by analyzing CSF. In addition the alterations in protein expression related to A-T will be quantified by liquid chromatography/mass spectrometry (LC/MS)-based proteomic analysis of CSF from healthy individuals and A-T patients to determine candidate proteins (new biomarkers) which relative expression levels could be used as surrogate marker of disease progression.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2013

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

October 28, 2014

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 7, 2014

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2015

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2017

Completed
Last Updated

August 31, 2021

Status Verified

August 1, 2021

Enrollment Period

2.2 years

First QC Date

October 28, 2014

Last Update Submit

August 30, 2021

Conditions

Ataxia Telangiectasia

Keywords

Ataxia Telangiectasiacerebrospinal fluidinflammationproteomic analysis

Outcome Measures

Primary Outcomes (1)

  • Concentration of IL-8 and oxidative stress in cerebrospinal fluid

    • To analyse functional gene expression of oxidative stress and low grade inflammation by means of RT-PCR and cytometric bead array.

    24 months

Secondary Outcomes (4)

  • Alterations in protein expression related to A-T

    24 months

  • Number of Participants with Adverse Events

    24 months

  • Alterations in protein expression levels in CSF compared with MRI findings in different age groups of classical A-T.

    24 months

  • Alterations in protein expression levels in CSF with MRI findings in different age groups of classical A-T. Candidate proteins whose relative expression levels could be used as surrogate marker of disease progression.

    24 months

Study Arms (2)

Ataxia Telangiectasia

OTHER

20 patients with clinically and/or genetically diagnosed Ataxia telangiectasia will get a lumbar puncture

Procedure: Lumbar puncture

Healthy Control

OTHER

20 patients without inflammation, infection or any other pathology of the CNS, in that a lumbar puncture is indicated for either diagnostic or therapeutic reason (i.e. for the exclusion of a meningitis, subarachnoid hemorrhage or in therapeutic liquor drain in idiopathic intracranial hypertension)

Procedure: Lumbar puncture

Interventions

Lumbar puncturePROCEDURE

Lumbar puncture is done according to general practice

Ataxia TelangiectasiaHealthy Control

Eligibility Criteria

Age2 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Aim group: clinically and/or genetically diagnosed Ataxia telangiectasia; Control group: neurologic non-inflammatory disease with an indication for diagnostic or therapeutic lumbar puncture
  • age between 2 and 40 years
  • written informed consent

You may not qualify if:

  • fever or clinical signs of an infection
  • leucocyte count \>12´000/µl and C reactive protein (CrP) \>2mg/dl
  • chronic diseases with need of immunomodulatory therapies (bronchial asthma, rheumatoid arthritis)
  • medication with statins
  • other diseases with influence in the immunosystem (i.e. diabetes mellitus, malignoma, renal failure requiring dialysis)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Johann Wolfgang Goethe University Hospitals

Frankfurt am Main, Hesse, 60590, Germany

Location

Related Publications (5)

  • Hoche F, Seidel K, Theis M, Vlaho S, Schubert R, Zielen S, Kieslich M. Neurodegeneration in ataxia telangiectasia: what is new? What is evident? Neuropediatrics. 2012 Jun;43(3):119-29. doi: 10.1055/s-0032-1313915. Epub 2012 May 21.

    PMID: 22614068BACKGROUND

  • Reichenbach J, Schubert R, Schindler D, Muller K, Bohles H, Zielen S. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid Redox Signal. 2002 Jun;4(3):465-9. doi: 10.1089/15230860260196254.

    PMID: 12215213BACKGROUND

  • McGrath-Morrow SA, Collaco JM, Crawford TO, Carson KA, Lefton-Greif MA, Zeitlin P, Lederman HM. Elevated serum IL-8 levels in ataxia telangiectasia. J Pediatr. 2010 Apr;156(4):682-4.e1. doi: 10.1016/j.jpeds.2009.12.007. Epub 2010 Feb 20.

    PMID: 20171651BACKGROUND

  • Zielen S, Schubert R. Workshop report: European workshop on ataxia-telangiectasia, Frankfurt, 2011. J Neurogenet. 2011 Oct;25(3):78-81. doi: 10.3109/01677063.2011.592553. Epub 2011 Jul 6.

    PMID: 21732725BACKGROUND

  • Dzieciatkowska M, Qi G, You J, Bemis KG, Sahm H, Lederman HM, Crawford TO, Gelbert LM, Rothblum-Oviatt C, Wang M. Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A-T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology. Int J Proteomics. 2011;2011:578903. doi: 10.1155/2011/578903. Epub 2011 Jun 23.

    PMID: 22084690BACKGROUND

Related Links

MeSH Terms

Conditions

Ataxia TelangiectasiaInflammation

Interventions

Spinal Puncture

Condition Hierarchy (Ancestors)

Spinocerebellar AtaxiasCerebellar AtaxiaCerebellar DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurocutaneous SyndromesAtaxiaDyskinesiasNeurologic ManifestationsTelangiectasisVascular DiseasesCardiovascular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesPrimary Immunodeficiency DiseasesDNA Repair-Deficiency DisordersMetabolic DiseasesNutritional and Metabolic DiseasesImmunologic Deficiency SyndromesImmune System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiopsySpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, NeurologicalPuncturesTherapeuticsSurgical Procedures, OperativeInvestigative Techniques

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Stefan Zielen, Prof. Dr.

Study Record Dates

First Submitted

October 28, 2014

First Posted

November 7, 2014

Study Start

April 1, 2013

Primary Completion

May 30, 2015

Study Completion

July 31, 2017

Last Updated

August 31, 2021

Record last verified: 2021-08

Locations

DE(1)