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Ectosomes, New Biomarkers of Tau Pathology? (ECTAUSOME)

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.
 
ClinicalTrials.gov Identifier: NCT03381482
Recruitment Status : Recruiting
First Posted : December 22, 2017
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:
In Alzheimer's disease (AD), neurofibrillary degeneration (NFD) is characterized by the intraneuronal aggregation of Tau proteins. The pathology progresses through a hierarchical pathway that may be associated with the intercellular transmission of pathology as demonstrated in our rat models. This transmission implies that Tau is actively secreted and may participate to the first steps of Tau pathology spreading. It is demonstrated in cell lines and animal models (rodents and non-human primates) that Tau is secreted not only in free forms but also in extracellular vesicles. If Tau is found in biological fluids before neuronal death it may represent an early marker of the NFD and will also define therapeutically targets. In this context, the aim is now to transfer this knowledge in humans and to decipher the nature of Tau secreted in plasma and cerebrospinal fluids collected from healthy controls to AD patients, and to decipher if the presence of tau inside vesicles is influenced by the pathology.

Condition or disease Intervention/treatment
Alzheimer Disease Diagnostic Test: CSF drawing during spinal anaesthesia Diagnostic Test: Fasting blood sample Diagnostic Test: Lumbar puncture

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Ectosomes, New Biomarkers of Tau Pathology?
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Controls
Group 1: the 4ml of CSF collected in the surgery context will be kept for the study, and 6x5ml of blood will be added to the usual samples.
Diagnostic Test: CSF drawing during spinal anaesthesia
4mL of CSF by lumbar puncture

Diagnostic Test: Fasting blood sample
6x5 mL of fasting blood sample

Asymptomatic cases with high risk to develop AD
Group 2: 10ml of CSF and 6x5ml of blood will be collected
Diagnostic Test: Fasting blood sample
6x5 mL of fasting blood sample

Diagnostic Test: Lumbar puncture
10 mL of CSF by lumbar puncture

Cases with isolated cognitive complaint
Group 3: 10ml of CSF and 6x5ml of blood will be collected
Diagnostic Test: Fasting blood sample
6x5 mL of fasting blood sample

Diagnostic Test: Lumbar puncture
10 mL of CSF by lumbar puncture

Prodromal AD
Group 4: 10ml of CSF and 6x5ml of blood will be collected
Diagnostic Test: Fasting blood sample
6x5 mL of fasting blood sample

Diagnostic Test: Lumbar puncture
10 mL of CSF by lumbar puncture

Mild to moderate probable AD-type dementia
Group 5: 10ml of CSF and 6x5ml of blood will be collected
Diagnostic Test: Fasting blood sample
6x5 mL of fasting blood sample

Diagnostic Test: Lumbar puncture
10 mL of CSF by lumbar puncture




Primary Outcome Measures :
  1. Presence of Tau in extracellular vesicles in CSF [ Time Frame: Baseline ]
    Tau will be measured by ELISA in extracellular vesicles and the presence of Tau in extracellular vesicles will considered positive if the concentration of Tau is superior to the sensitivity threshold of the antibody used.


Secondary Outcome Measures :
  1. The ratio of free Tau/vesicular Tau for all groups will be assessed with samples obtained during the visit. [ Time Frame: Baseline ]
    Tau will be measured by ELISA (concentration of Tau in pg/mL) and using the Nanosight technology (% of vesicles containing Tau). Results will be expressed either in percentage or in concentration (ie concentration of free Tau/concentration of vesicular Tau; % of free Tau/% of vesicular Tau).

  2. The presence of clusters of the epigenetic markers H3K9me3 in nuclei of peripheral blood mononuclear cells for all groups will be assessed with samples obtained during the visit. [ Time Frame: Baseline ]
    The H3K9m3 marker will be revealed by immunodetection and revealed by fluorescence. The presence of one cluster of H3K9m3 will be considered as positive. Results will be expressed in % of cells with clusters.


Biospecimen Retention:   Samples With DNA
blood and CSF sampling


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Subjects intended to participate in group 1 have to undergo a lumbar puncture for other reasons than a cognitive complaint. They will be identified in the anaesthesiology department among patients who are waiting for scheduled orthopaedic surgery needing spinal anaesthesia. They will have the sample collection done with its specific procedures in the same time.

if a subject is already followed at the MRRC and meets group 1 eligibility criteria, he/she could be asked to participate in the study and thus be enrolled and followed by a MRRC investigator.

Patients intended to participate in groups 2 to 5 will be identified at the MRRC during their scheduled visit with the investigators specialized in neurology/geriatric medicine.

Criteria

Inclusion Criteria:

  • Subjects able to undergo a lumbar puncture;
  • Subjects who have a partner who will be required for driving back the subject after the lumbar punction for safety reasons (not required for control subjects);
  • Subjects (or the study partner for group 5) capable of and willing to comply with the protocol and to give their written informed consents after having received and understood the subject information. According to the legal protection or the mental capacities of the subject, he/she will be accompanied by him/her legally acceptable representative during this procedure;
  • Blood coagulation testing
  • Subjects registered with the French Social Security, in agreement with the French law on biomedical experimentation.

Group 1: controls

  • absence of cognitive complaint
  • absence of significant cognitive impairment: MMSE>27
  • Negative ApoE4 status (ε 4-/ ε 4-) No family history of AD at first degree Group 2: asymptomatic cases with high risk to develop AD
  • absence of cognitive complaint
  • absence of significant cognitive impairment : MMSE>27
  • known ApoE4 status or family history of AD at first degree Group 3: cases with isolated cognitive complaint
  • presence of a cognitive complaint
  • absence of cognitive impairment assessed by MMSE>27 and standard neuropsychological examination (performed < 1 year) Group 4: prodromal AD according to the 2007 criteria (Dubois et al., 2007)
  • progressive and significant episodic memory impairment >6 months
  • And at least one of the following: medial temporal atrophy of brain MRI / low Ab42 and increased total and phosphorylated Tau protein in the CSF/ bilateral temporoparietal hypometabolism on brain FDG-PET/ positive amyloid brain PET if available
  • exclusion of any differential diagnoses Group 5: Mild to moderate probable AD-type dementia according to the NIA 2011 criteria
  • progressive and significant cognitive decline >6 months
  • amnestic or any other predominant clinical presentation
  • exclusion of any differential diagnoses
  • MMSE between 15 and 26 (inclusive)

Exclusion Criteria:

  • Subjects with dementia caused by a non-neurodegenerative disease, including patients with severe cerebrovascular risk factor load;

Associated Illnesses or conditions:

  • Subjects with other neurodegenerative disease such as fronto-temporal dementia (FTD), Lewy body dementia and Parkinson's disease;
  • Subjects with other serious neurological disorder such as brain tumour, stroke, epilepsy, hydrocephalus and any condition which contraindicates, in the investigator's judgment, entry to the study;
  • Subjects with demyelinating diseases of the peripheral nervous system such as Guillain-Barre Syndrome;

Biological exclusion criteria:

  • Subjects with known active Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV);
  • Subjects with clinical or significant laboratory abnormalities, in the judgment of the investigator;

Others:

  • Subjects with excessive alcohol intake or drug abuse, in the judgment of the investigator;
  • Subjects who have contraindications to perform a lumbar puncture;
  • Subjects who, in the opinion of the Investigator, have a risk of non-compliance to the study procedures or who are otherwise not appropriate to include in this clinical trial (for example, being impossible to contact in case of emergency).

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): NCT03381482


Contacts
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Contact: Vincent DERAMECOURT, MD,PhD 320446021 ext +33 vincent.deramecourt@chru-lille.fr

Locations
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France
Hôpital Roger Salengro, CHRU Recruiting
Lille, France
Principal Investigator: Vincent DERAMEUCOURT, MD,PhD         
Sponsors and Collaborators
University Hospital, Lille
Investigators
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Principal Investigator: Vincent DERAMECOURT, MD,PhD University Hospital, Lille
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT03381482    
Other Study ID Numbers: 2016_59
2017-A01715-48 ( Other Identifier: ID-RCB number, ANSM )
First Posted: December 22, 2017    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020

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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 University Hospital, Lille:
Alzheimer disease
Extracellular vesicles
Biomarker
Tau
CSF
Plasma
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs