- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05746715
A Natural History Study of Preclinical Genetic Creutzfeldt-Jakob Disease (CJD) (NHS_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.
Study Overview
Status
Conditions
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Noa Bregman, MD
- Phone Number: +972527360163
- Email: noabr@tlvmc.gov.il
Study Locations
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Tel Aviv, Israel, 64239
- Recruiting
- Cognitive Neurology Unit
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Contact:
- Noa Bregman, MD
- Phone Number: +972527360163
- Email: noabr@tlvmc.gov.il
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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genetic Creutzfeldt-Jakob Disease (CJD) patients
A group of patients diagnosed with CJD, who are carriers of E200K mutation in the PRNP gene (gCJD)
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Healthy first degree relatives
A group of first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Existence of pathological Prion Protein (PrP) in CSF of mutation carriers
Time Frame: 8 years
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CSF fluid obtained through yearly lumbar puncture of healthy relatives will be explored for the existence of PrP using RTQuic
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8 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Diffusion Tensor Imaging collected using yearly MRI scans in healthy relatives
Time Frame: 8 years
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Analysis of Diffusion Tensor Imaging (DTI) is expected to reveal lower diffusivity and higher fraction anisotropy in prodromal gCJD
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8 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Noa Bregman, MD, Tel Aviv Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0215-18
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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