The Generative Brain

The Role of the Coagulation Pathway at the Synapse in Prion Diseases (Sheba Medical Center, NCT02480725)

NCT02480725 is an observational study registered in June 2015 by Sheba Medical Center in Israel, with the Goettingen prion referral centre under Inga Zerr as collaborator. It set out to measure thrombin activity in cerebrospinal fluid (CSF) of people with Creutzfeldt-Jakob disease (CJD), people with other dementias and control samples, using a fluorogenic substrate assay in Joab Chapman's laboratory at Sheba. The idea is that prion damage may partly run through coagulation enzymes such as thrombin, so CSF coagulation activity might mark disease onset in high risk carriers such as E200K and track progression. The registry record has not been touched since June 2015 and its status is Unknown, so it is stale. No published thrombin results in CJD or prion disease were found. The same group did publish a CSF thrombin assay method in 2021, tested in infection rather than prion disease. Information only.

Status as of 2026-10-17. Please check the study registry for the latest position.

Key facts

  • The registry record names Sheba Medical Center as sponsor (local id 1702-14 SMC), the University of Goettingen Prion Referral Center under Prof. Zerr as collaborator, and Dr. Oren Cohen of Sheba as principal investigator.
  • Design is an observational prospective cohort of an estimated 50 people aged 35 to 90 who have a lumbar puncture as part of a cognitive decline workup, in three groups: CJD, non-CJD dementia, and non-CJD control CSF; people on anticoagulants are excluded.
  • The description also plans a retrospective assay of 100 to 200 stored CJD CSF samples with matched controls, with samples coming from Sheba and the Goettingen group.
  • The primary outcome is CSF thrombin activity, measured by cleavage of a fluorogenic peptide substrate in Prof. Chapman's laboratory at Sheba, with a 10 year time frame; MMSE and FAB cognitive scores are taken in the patient groups.
  • The stated rationale is that coagulation serine proteases such as thrombin may partly mediate prion brain damage, so CSF coagulation activity could mark onset in E200K and other high risk carriers, track progression, and point to a treatment target.
  • Status is Unknown with last known status Not yet recruiting; the record was first posted on 24 June 2015, last updated on 23 June 2015 and last verified in June 2015, with completion estimated for July 2025; no results are posted.
  • The Sheba and Tel Aviv University group around Joab Chapman, Nicola Maggio and Efrat Shavit-Stein published a sensitive CSF thrombin and activated protein C activity assay in 2021, tested on 14 normal pressure hydrocephalus controls and 7 CNS infection cases; the paper does not mention CJD or prions.
  • The synaptic part of the title draws on the group's earlier work showing thrombin acts on neurons mainly through the receptor PAR1 and shifts the threshold for synaptic plasticity; their 2015 review does not mention prion disease.
  • A Europe PMC search of papers co-authored by Oren S. Cohen and Joab Chapman finds about 25 E200K and CJD papers from 2009 to 2024 on MRI, EEG, sleep, CSF tau and clinical course, none on thrombin or coagulation.
  • Earlier CSF work by the same investigators found CSF tau tracks the extent of cortical MRI change in 44 E200K patients (2016) and disease duration in 69 familial CJD patients (2019).
  • Joab Chapman is described as head of neurology at Sheba since 2002 and holder of the Harden chair at the Tel Aviv University medical faculty.

Timeline

  1. 2015Sheba and Tel Aviv University group publishes a review on thrombin and PAR1 in synaptic plasticity.
  2. 2015NCT02480725 submitted (22 June) and posted (24 June); study start given as June 2015; last update and last verification of the record.
  3. 2016Same investigators publish CSF tau versus cortical MRI involvement in E200K CJD, with no thrombin data.
  4. 2021Group publishes its CSF thrombin and activated protein C assay in Neural Regeneration Research, without prion samples.
  5. 2024Estimated primary completion date in the registry passes with no update.
  6. 2025Estimated study completion date in the registry passes with no update or results.
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