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The Role of the Coagulation Pathway at the Synapse in Prion Diseases

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ClinicalTrials.gov Identifier: NCT02480725
Recruitment Status : Not yet recruiting
First Posted : June 24, 2015
Last Update Posted : June 24, 2015
Sponsor:
Collaborator:
Prof. Zerr , Prion Referral Center , University of Gottingen, Germany
Information provided by (Responsible Party):
Dr. Oren Cohen, Sheba Medical Center

Brief Summary:

The study hypothesis is that that the deleterious effect of prions on the brain may be mediated (at least partially) by activation of serine proteases involved in the coagulation system. If this is true, then measurement of the activity of the coagulation system may be a marker of disease onset (in at higher risk individuals such as E200K* carriers) and for disease progression or activity in affected individuals. In addition, modulation of the coagulation system activity may be a potential tool for therapeutic intervention.

*E200K- E200K mutation (Glu to Lys substitution) in the prion protein gene


Condition or disease Intervention/treatment
Creutzfeldt-Jakob Syndrome Procedure: collect CSF (Cerebrospinal fluid) sample

Detailed Description:

We plan to collect Cerebrospinal fluid (CSF) samples for thrombin activity assay in order to test whether there is a difference in thrombin activity in the CSF between CJD (Creutzfeldt-Jakob disease) and non-CJD patients. CSF samples will be obtained from two sources 1. Patients with familial or sporadic CJD and control patients with other neurodegenerative disorders (e.g. SDAT**, NPH) that will be evaluated in Sheba Medical Center 2. From our collaborating group of Prof. Zerr in the German Prion Referral Center at the University of Gottingen which has a collection of thousands of CSF samples from patients with familial and sporadic CJD as well as ideal controls with other degenerative brain disease.

The study has 2 sections:

  1. Prospective part in which we plan to recruit 25 patients with CJD and 25 patients with other types of dementia from Sheba Medical Center (SMC). Prior to inclusion in the study a senior neurologist will interview the patient and will verify that he fully understands the objectives of the study and he is mentally qualified to sign the informed consent form (severely demented patients who will not be able to adequately consider the participation in the study will be excluded).

    Cognitive performance will be evaluated using the Mini-mental Status Examination and Frontal Assessment Battery scales.

    No clinical data other than the cognitive assessment and those needed for the clinical work up will be especially collected for this study.

  2. Retrospective part in which CSF samples from CJD patients and patients with other type of dementia will be shipped to us from our collaborators in Germany ans will be assayed for Thrombin activity. We plan to recruit to this part of the study 100-200 CJD patient CSF samples and a same number of samples from age matched controls.

Thrombin activity (for samples from both parts of the study) will be assayed as follows: CSF sample will be placed in a black 96 well dish (10 per well). Thrombin activity will be measured by a fluorometric assay, quantifying the cleavage of the synthetic peptide substrate Boc-Asp(OBzl)-Pro-Arg-AMC*** (I-1560, Bachem, Switzerland, 13 molar final concentration). Measurements will be performed by the Infinite 2000 microplate reader (Tecan, infinite 200, Switzerland) with excitation and emission filters of 360±35 and 460±35 nm, respectively. CSF testing for thrombin activity will be conducted in Professor Chapman's laboratory in Sheba. This laboratory is actively engaged in research on the role of thrombin and PAR-1 in diseases of the nervous system and is fully equipped to perform the biochemical and protein levels experiments.

The assay has the potential for commercialization as a diagnostic test for CJD. In addition, there is the potential to develop therapeutic agents targeting excessive thrombin activation.

**SDAT=Senile Dementia of Alzheimer Type

***AMC= Amino Methyl Coumarin


Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of the Coagulation Pathway at the Synapse in Prion Diseases
Study Start Date : June 2015
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Thrombin

Group/Cohort Intervention/treatment
CJD (Creutzfeldt-Jakob disease) patients

Prior to inclusion in the study a senior neurologist will interview the patient and will verify that he fully understands the objectives of the study and he is mentally qualified to sign the informed consent form (severely demented patients who will not be able to adequately consider the participation in the study will be excluded).

Cognitive performance will be evaluated using the Mini-mental Status Examination and Frontal Assessment Battery scales.

No clinical data other than the cognitive assessment and those needed for the clinical work up will be especially collected for this study.

We plan to collect CSF samples for thrombin activity assay.

non-CJD patients with a type of dementia

Prior to inclusion in the study a senior neurologist will interview the patient and will verify that he fully understands the objectives of the study and he is mentally qualified to sign the informed consent form (severely demented patients who will not be able to adequately consider the participation in the study will be excluded).

Cognitive performance will be evaluated using the Mini-mental Status Examination and Frontal Assessment Battery scales.

No clinical data other than the cognitive assessment and those needed for the clinical work up will be especially collected for this study.

We plan to collect CSF samples for thrombin activity assay.

Procedure: collect CSF (Cerebrospinal fluid) sample
collecting CSF samples for thrombin activity assay

CSF samples of non-CJD patient used as control
CSF samples : Thrombin activity will be assayed.



Primary Outcome Measures :
  1. Thrombin activity assay [ Time Frame: 10 years ]

Biospecimen Retention:   Samples Without DNA
CSF samples


Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
CJD and non-CJD patients
Criteria

Inclusion Criteria:

  • Patient undergoing lumbar puncture test as part of the investigation of cognitive decline.

Exclusion Criteria:

  • Patients on anticoagulation or those who have contraindication for undergoing lumbar puncture.

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): NCT02480725


Contacts
Contact: Oren Cohen, Dr. (MD) +972-52-6667584 coheno@asaf.health.gov.il

Sponsors and Collaborators
Sheba Medical Center
Prof. Zerr , Prion Referral Center , University of Gottingen, Germany
Investigators
Principal Investigator: Oren Cohen, Dr. (MD) Cheba Medical Center

Publications:

Responsible Party: Dr. Oren Cohen, MD, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02480725     History of Changes
Other Study ID Numbers: 1702-14 SMC
First Posted: June 24, 2015    Key Record Dates
Last Update Posted: June 24, 2015
Last Verified: June 2015

Keywords provided by Dr. Oren Cohen, Sheba Medical Center:
CJD
CSF
prion
thrombin

Additional relevant MeSH terms:
Prion Diseases
Creutzfeldt-Jakob Syndrome
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Dementia
Brain Diseases
Neurocognitive Disorders
Mental Disorders
Thrombin
Hemostatics
Coagulants