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Ccf mtDNA as a Neurodegenerative Biomarker

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. Identifier: NCT03938909
Recruitment Status : Recruiting
First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Information provided by (Responsible Party):
Stefano Gambardella, Neuromed IRCCS

Brief Summary:

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. One of the most critical factors in biomarker research is the inadequate linkage of biological samples with data from medical records, environmental exposure, lifestyle information and other medically relevant information. In this context the biobanks are an invaluable resource for medical research and, in particular, for the identification of biomarkers. This project aims to enstablish a biobank for Multiple Sclerosis that allow to collect periodically, at each follow up, clinical data, tissues such as blood and cerebrospinal fluid and DNA, RNA, proteins, from patients afferent at the Centre for the Study and Cure of Multiple Sclerosis in Neurological Institute "Neuromed", Pozzilli, Isernia. The samples stored in this biobank are examined by quantization of a potential innovative biomarker focused on the formation of circulating mitochondrial DNA. Fragments of mitochondrial DNA (mtDNA) are released outside the cell and they appear to persist in extracellular fluids as circulating, cell-free, mtDNA (ccf-mtDNA).

This occurs during acute inflammation, which anticipates the neurodegenerative process. Thus, an increase in inflammatory cells in the affected regions is expected to add on mtDNA release into the CSF. Thus, ccf-mtDNA may represent a powerful biomarker for disease screening and prognosis at early stage, although its biological role may extend to generating the neurobiology of disease.


  1. Identify a technique that allows to isolate, the mitochondrial DNA circulating from different biological tissues (Droplet Digital PCR, Real Time PCR).
  2. Use different technologies to quantify the presence of circulating mitochondrial DNA
  3. Use circulating mitochondrial DNA as a biomarker of neurodegenerative and / or neuroinflammatory pathologies.

It is essential to understand the tissue specific origin of circulating mtDNA for both diagnostic and therapeutic considerations. . We believe that our current knowledge on cell free circulating mtDNA is in a rather exploratory phase with a potential for the future to rewrite the pathology of the leading causes of morbidity and mortality such as inflammatory conditions, autoimmune disorders, cancer, heart disease, stroke and injury.

Condition or disease Intervention/treatment
Neurodegenerative Diseases Genetic: cif mtDNA biomarker

  Show Detailed Description

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 2000 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: Ccf mtDNA as a Biomarker in Neurological and Neurodegenerative Diseases
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : September 1, 2019
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
Patients with Multiple Sclerosis
200 patients and 200 control
Genetic: cif mtDNA biomarker
The aim is to evaluate the role of ccf-mtDNA as a specific and early biomarker for different clinical pictures

Patients with dementia
100 patients and 100 control
Genetic: cif mtDNA biomarker
The aim is to evaluate the role of ccf-mtDNA as a specific and early biomarker for different clinical pictures

Patients with Parkinson's disease
50 patients and 50 control
Genetic: cif mtDNA biomarker
The aim is to evaluate the role of ccf-mtDNA as a specific and early biomarker for different clinical pictures

Primary Outcome Measures :
  1. Neurology consulting [ Time Frame: 1 week ]
    Radiological and neuro and physiological approces; different laboratory test (CSF analysis,ematological test);neurological impairment is assessed with Expanded Disability Status Scale and through radiological assessment, cognitive impairment.

Secondary Outcome Measures :
  1. Molecular testing [ Time Frame: 1 years ]
    Molecular analysis of ccf mtDNA

  2. Cytokine measurements [ Time Frame: 1 years ]
    The plasma levels of GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL- 8, IL-10, and TNF-α will be measured using the Human Cytokine Magnetic 10-Plex Panel (Thermo Fisher Scientific) according to the manufacturer's instructions. We will add the same plasma sample to each plate for cytokine multiplex assay and calculated inter assay CV (%). The quantization of plasma cytokines will be compared with the quantization of the ccf mtDNA and the clinical stage of the pathology

  3. Statistical analyses. [ Time Frame: 5 months ]
    Data will be presented as the mean ± standard deviation (SD). Categorical variables will compared using a chi-squared test. For a comparison of averages for the two groups, a Student's t-test will be used. When the data set will not normally distributed, a Mann-Whitney U-test will be used. Analysis of covariance (ANCOVA) controlling for age and sex will examined to evaluate the effects of age and sex on CFS, plasma or serum mtDNA copy number and cytokine levels. For a comparison of four groups, a one-way analysis of variance (ANOVA) followed by multiple comparisons with Tukey's method will used. Correlation coefficients between mtDNA copy number in plasma and cytokines will be calculated using Spearman's rank correlation coefficients. A P-value < 0.05 will considered as statistically significant and will corrected for multiple comparisons using Bonferroni's method.

Biospecimen Retention:   Samples With DNA
CSF, Serum, Plasma, Blood, DNA and RNA

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
neurology analysis of patients by international trembling guidelines

Inclusion Criteria:

• Clinical criteria for neurogenetic disease

Exclusion Criteria:

• absence of clinical condition

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 identifier (NCT number): NCT03938909

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Contact: Stefano Gambardella, PhD +39 0865 915 209

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Stefano Gambardella Recruiting
Pozzilli, Isernia, Italy, 86077
Contact: Stefano Gambardella, PhD    +39 0865 915 209   
Sponsors and Collaborators
Neuromed IRCCS

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Responsible Party: Stefano Gambardella, Doctor, Principal Investigator, Neuromed IRCCS Identifier: NCT03938909     History of Changes
Other Study ID Numbers: CGM-03
First Posted: May 6, 2019    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Neurodegenerative Diseases
Nervous System Diseases