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

June 23, 2015 updated by: Dr. Oren Cohen, Sheba Medical Center

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

33 years to 88 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

CJD and non-CJD patients

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Thrombin activity assay
Time Frame: 10 years
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheba Medical Center

Collaborators

Prof. Zerr , Prion Referral Center , University of Gottingen, Germany

Investigators

  • Principal Investigator: Oren Cohen, Dr. (MD), Cheba Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Anticipated)

July 1, 2024

Study Completion (Anticipated)

July 1, 2025

Study Registration Dates

First Submitted

June 22, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 24, 2015

Study Record Updates

Last Update Posted (Estimate)

June 24, 2015

Last Update Submitted That Met QC Criteria

June 23, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1702-14 SMC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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