Ataxia TelangiectasiaNCT02285348
Oxidative Stress, Low Grade Inflammation, Tissue Breakdown and Biomarkers in Cerebrospinal Fluid of A-T
A study testing Lumbar puncture in people with Ataxia Telangiectasia, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
Trial summary
Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. Read more about this study
- Who is it for?
- Ages 2 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Ataxia Telangiectasia
- What is being tested?
- Lumbar puncture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2013to 31 Jul 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Johann Wolfgang Goethe University Hospitals
Frankfurt am Main, Hesse, 60590
About this study
Official title: Oxidative Stress, Low Grade Inflammation, Tissue Breakdown and Biomarkers in Cerebrospinal Fluid of Patients With Ataxia Telangiectasia
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.
Read the detailed description
Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. For clinicians and scientists the underlying mechanism and process of neurodegeneration leading to loss of cerebellar neurons and neurological function is largely unknown. In addition no surrogate marker of neurological degeneration and disease progression exist.
Three major factors may be responsible for progression of neurodegeneration:
- A-T patients exhibit elevated levels of reactive oxygen species (ROS) and reduced anti-oxidative capacity. It has been proposed that ROS is responsible for destruction of the purkinje cells in the cerebellum.
- Ongoing low grade inflammation due to immunodeficiency. Elevated serum interleukin-8 (IL-8) levels in patients with A-T are postulated that systemic inflammation may contribute to the disease phenotype. How inflammation and neurodegeneration interact is, however, a matter of ongoing debate.
- Low levels of growth hormones (GH). Extracerebellar MRI - lesions in A-T go along with deficiency of the GH axis, high Ataxia scores and advanced age.
The aim of the proposal is to investigate oxidative stress, low grade inflammation, tissue breakdown and biomarkers in cerebrospinal fluid (CSF), a fluid that is in direct contact with central nervous system (CNS), of A-T patients.
- To analyse functional gene expression of oxidative stress and low grade inflammation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and cytometric bead array.
- To characterize the alterations in protein expression related to A-T, a LC/MS-based quantitative proteomic analysis of CSF from control and A-T patients
- To compare alterations in protein expression levels in CSF with MRI findings in different age groups of classical A-T.
- To determine candidate proteins whose relative expression levels could be used as surrogate marker of disease progression?
- To established an analysis system on a basis of multiplex ELISA-technique to evaluate potential candidates/surrogate markers for disease progression in a larger cohort of patients.
- Conditions
- Ataxia Telangiectasia
- Being tested
- Lumbar puncture
- Keywords
- Ataxia Telangiectasia, cerebrospinal fluid, inflammation, proteomic analysis
- Medical subject headings
- Ataxia Telangiectasia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lumbar punctureProcedure or surgery
Lumbar puncture is done according to general practice
| Study group | Role | What they receive |
|---|---|---|
| Ataxia Telangiectasia | Other | 20 patients with clinically and/or genetically diagnosed Ataxia telangiectasia will get a lumbar puncture Receives: 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) Receives: Procedure: Lumbar puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (4)
Alterations in protein expression related to A-T
- Alterations in protein expression related to A-T, a LC/MS-based quantitative proteomic analysis of CSF from controls and A-T patients
Measured: 24 months
Number of Participants with Adverse Events
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: 24 months
Alterations in protein expression levels in CSF compared with MRI findings in different age groups of classical A-T.
Measured: 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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2014 (estimated)
- Study start1 Apr 2013
- Primary completion30 May 2015
- Study completion31 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Ataxia TelangiectasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johann Wolfgang Goethe University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefan Zielen, Johann Wolfgang Goethe University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02285348
- Sponsor's protocol ID
- FRA-AT.CSF.2012
- Status last verified
- Aug 2021
- First submitted
- 28 Oct 2014
- Last updated
- 31 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22614068Reichenbach 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.
PubMed 12215213McGrath-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.
PubMed 20171651Zielen 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.
PubMed 21732725Dzieciatkowska 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.
PubMed 22084690
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Stress, Low Grade Inflammation, Tissue Breakdown and Biomarkers in Cerebrospinal Fluid of Patients With Ataxia Telangiectasia
- ClinicalTrials.gov ID
- NCT02285348
- Acronym / sponsor ID
- FRA-AT.CSF.2012
- Conditions
- Ataxia Telangiectasia
- Keywords
- Ataxia Telangiectasia, cerebrospinal fluid, inflammation, proteomic analysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Johann Wolfgang Goethe University HospitalUniversity, hospital or other
- Study start
- 1 Apr 2013 (actual)
- Primary completion
- 30 May 2015 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 7 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. For clinicians and scientists the underlying mechanism and process of neurodegeneration leading to loss of cerebellar neurons and neurological function is largely unknown. In addition no surrogate marker of neurological degeneration and disease progression exist.
Three major factors may be responsible for progression of neurodegeneration:
- A-T patients exhibit elevated levels of reactive oxygen species (ROS) and reduced anti-oxidative capacity. It has been proposed that ROS is responsible for destruction of the purkinje cells in the cerebellum.
- Ongoing low grade inflammation due to immunodeficiency. Elevated serum interleukin-8 (IL-8) levels in patients with A-T are postulated that systemic inflammation may contribute to the disease phenotype. How inflammation and neurodegeneration interact is, however, a matter of ongoing debate.
- Low levels of growth hormones (GH). Extracerebellar MRI - lesions in A-T go along with deficiency of the GH axis, high Ataxia scores and advanced age.
The aim of the proposal is to investigate oxidative stress, low grade inflammation, tissue breakdown and biomarkers in cerebrospinal fluid (CSF), a fluid that is in direct contact with central nervous system (CNS), of A-T patients.
- To analyse functional gene expression of oxidative stress and low grade inflammation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and cytometric bead array.
- To characterize the alterations in protein expression related to A-T, a LC/MS-based quantitative proteomic analysis of CSF from control and A-T patients
- To compare alterations in protein expression levels in CSF with MRI findings in different age groups of classical A-T.
- To determine candidate proteins whose relative expression levels could be used as surrogate marker of disease progression?
- To established an analysis system on a basis of multiplex ELISA-technique to evaluate potential candidates/surrogate markers for disease progression in a larger cohort of patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ataxia Telangiectasia | Other | Procedure: Lumbar puncture20 patients with clinically and/or genetically diagnosed Ataxia telangiectasia will get a lumbar puncture |
| Healthy Control | Other | Procedure: Lumbar puncture20 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) |
Who may qualify
- Ages
- 2 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lumbar punctureLumbar puncture is done according to general practice | Procedure or surgery | Ataxia Telangiectasia, Healthy Control |
Primary outcome
Concentration of IL-8 and oxidative stress in cerebrospinal fluid
Time frame: 24 months
• To analyse functional gene expression of oxidative stress and low grade inflammation by means of RT-PCR and cytometric bead array.
4 secondary outcomes
Alterations in protein expression related to A-T
Time frame: 24 months
Number of Participants with Adverse Events
Time frame: 24 months
Alterations in protein expression levels in CSF compared with MRI findings in different age groups of classical A-T.
Time frame: 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.
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2021.
- Background: PubMed 22614068Hoche 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.
- Background: PubMed 12215213Reichenbach 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.
- Background: PubMed 20171651McGrath-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.
- Background: PubMed 21732725Zielen 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.
- Background: PubMed 22084690Dzieciatkowska 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lumbar puncture in people with Ataxia Telangiectasia, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of IL-8 and oxidative stress in cerebrospinal fluid (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02285348, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2021.