Creutzfeldt-Jakob Disease (CJD)NHS_CJDNCT05746715
A Natural History Study of Preclinical Genetic Creutzfeldt-Jakob Disease (CJD)
An observational study of Creutzfeldt-Jakob Disease (CJD), run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Creutzfeldt-Jakob Disease (CJD)
- How many people
- 126 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jun 2022to 30 May 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A group of patients diagnosed with CJD, who are carriers of E200K mutation in the PRNP gene (gCJD), and 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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Cognitive Neurology Unit
Tel Aviv, 64239
Noa Bregman, MD, +972527360163, noabr@tlvmc.gov.il
About this study
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.
- Conditions
- Creutzfeldt-Jakob Disease (CJD)
- Keywords
- Creutzfeldt-Jakob Disease, Prion disease, E200K mutation
- Medical subject headings
- Creutzfeldt-Jakob Syndrome, Prion Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| genetic Creutzfeldt-Jakob Disease (CJD) patients | A group of patients diagnosed with CJD, who are carriers of E200K mutation in the PRNP gene (gCJD) | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Existence of pathological Prion Protein (PrP) in CSF of mutation carriers
CSF fluid obtained through yearly lumbar puncture of healthy relatives will be explored for the existence of PrP using RTQuic
Measured: 8 years
Secondary outcomes (1)
Changes in Diffusion Tensor Imaging collected using yearly MRI scans in healthy relatives
Analysis of Diffusion Tensor Imaging (DTI) is expected to reveal lower diffusivity and higher fraction anisotropy in prodromal gCJD
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2023
- Study start1 Jun 2022
- Primary completion30 Dec 2028 (estimated)
- Study completion30 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Creutzfeldt-Jakob Disease (CJD)Studies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Eli Sprecher, MD, Tel-Aviv Sourasky Medical Center
- Investigators
- Noa Bregman, MD, Principal investigator, Tel Aviv Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05746715
- Sponsor's protocol ID
- 0215-18
- Acronym
- NHS_CJD
- Status last verified
- Feb 2023
- First submitted
- 15 Feb 2023
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Omer N, Droby A, Silbak R, Trablus N, Bar David A, Shiner T, Alcalay Y, Alcalay R, Nathan T, Thaler A, Mirelman A, Gana Weisz M, Goldstein O, Glinka T, Orr-Urtreger A, Giladi N, Bregman N. White matter abnormalities in healthy E200K carriers may serve as an early biomarker for genetic Creutzfeldt-Jakob disease (gCJD). J Neurol Neurosurg Psychiatry. 2025 Mar 13;96(3):226-230. doi: 10.1136/jnnp-2024-333751.
PubMed 39084863Bregman N, Shiner T, Kave G, Alcalay R, Gana-Weisz M, Goldstein O, Glinka T, Aizenstein O, Bashat DB, Alcalay Y, Mirelman A, Thaler A, Giladi N, Omer N. The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol. BMC Neurol. 2023 Apr 14;23(1):151. doi: 10.1186/s12883-023-03193-8.
PubMed 37069531
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Natural History Study of Preclinical Genetic Creutzfeldt-Jakob Disease (CJD)
- ClinicalTrials.gov ID
- NCT05746715
- Acronym / sponsor ID
- NHS_CJD / 0215-18
- Conditions
- Creutzfeldt-Jakob Disease (CJD)
- Keywords
- Creutzfeldt-Jakob Disease, Prion disease, E200K mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 30 Dec 2028 (estimated)
- Study completion
- 30 May 2029 (estimated)
- First posted
- 28 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| genetic Creutzfeldt-Jakob Disease (CJD) patients | – | –A group of patients diagnosed with CJD, who are carriers of E200K mutation in the PRNP gene (gCJD) |
| 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A group of patients diagnosed with CJD, who are carriers of E200K mutation in the PRNP gene (gCJD), and 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- a clinical diagnosis of CJD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
1 secondary outcome
Changes in Diffusion Tensor Imaging collected using yearly MRI scans in healthy relatives
Time frame: 8 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Derived from this study: PubMed 39084863Omer N, Droby A, Silbak R, Trablus N, Bar David A, Shiner T, Alcalay Y, Alcalay R, Nathan T, Thaler A, Mirelman A, Gana Weisz M, Goldstein O, Glinka T, Orr-Urtreger A, Giladi N, Bregman N. White matter abnormalities in healthy E200K carriers may serve as an early biomarker for genetic Creutzfeldt-Jakob disease (gCJD). J Neurol Neurosurg Psychiatry. 2025 Mar 13;96(3):226-230. doi: 10.1136/jnnp-2024-333751.
- Derived from this study: PubMed 37069531Bregman N, Shiner T, Kave G, Alcalay R, Gana-Weisz M, Goldstein O, Glinka T, Aizenstein O, Bashat DB, Alcalay Y, Mirelman A, Thaler A, Giladi N, Omer N. The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol. BMC Neurol. 2023 Apr 14;23(1):151. doi: 10.1186/s12883-023-03193-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Noa Bregman, MD principal investigator
Tel Aviv Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Creutzfeldt-Jakob Disease (CJD), run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Noa Bregman, MD (+972527360163, NOABR@TLVMC.GOV.IL), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Existence of pathological Prion Protein (PrP) in CSF of mutation carriers (time frame: 8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05746715, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.