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NCT Number: NCT05746715

A Natural History Study of Preclinical Genetic Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.

The study includes two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year (for 4 years), healthy participants are invited for an "in-depth" visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture, and Polysomnography sleep lab (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a "brief" visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one "in-depth" visit, similar to the baseline visit of healthy relatives.

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Key information

Conditions

Creutzfeldt-Jakob Disease (CJD) Brain Diseases Central Nervous System Diseases Central Nervous System Infections Creutzfeldt-Jakob Syndrome Dementia Infections Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Prion Diseases

Age range

50 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • First--degree relative of an E200K gCJD patient.
  • Age 50 years or older at baseline.
  • Willingness to undergo genetic testing.
  • Ability to provide written informed consent under GCP, ICH, and local regulations.
  • Willingness and ability to comply with scheduled visits, required study procedures, and laboratory tests.

Exclusion criteria

  • a clinical diagnosis of CJD
  • Any other medical or psychiatric condition or laboratory abnormality, which in the opinion of the investigator might preclude participation.
  • Previously obtained MRI scan with evidence of clinically significant neurological disorder other than CJD.
  • Current anticoagulant treatment (e.g Non-vitamin K Antagonist Oral Anticoagulants (NOACs), Warfarin, Low Molecular weight Heparin) that might preclude safe completion of LP.
  • Conditions that preclude the safe performance of LP, such as severe lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
  • Conditions that preclude the safe performance of MRI scannings such as subjects who have a pacemaker, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body, or any other known contra-indication for MRI.
  • Active malignant disease.

Treatment and study plan

Primary outcomes

  1. Existence of pathological Prion Protein (PrP) in CSF of mutation carriers

    Time frame: 8 years

    CSF fluid obtained through yearly lumbar puncture of healthy relatives will be explored for the existence of PrP using RTQuic

Secondary outcomes

  1. Changes in Diffusion Tensor Imaging collected using yearly MRI scans in healthy relatives

    Time frame: 8 years

    Analysis of Diffusion Tensor Imaging (DTI) is expected to reveal lower diffusivity and higher fraction anisotropy in prodromal gCJD

Study contacts

Contact information is provided by the study sponsor or research team.

Noa Bregman, MD

CONTACT

[email protected]

+972527360163

Sponsors and collaborators

Lead sponsor

Tel-Aviv Sourasky Medical Center

Other Gov

Registry information

Acronym: NHS_CJD

Important dates

Study start
2022
Primary completion
2028
Study completion
2029
First posted
Feb 28, 2023
Registry last updated
Feb 28, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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