Multimodal Markers of Neurodegenerative Disorders at Presymptomatic Stages (NEUROPREMS)

July 17, 2024 updated by: Paris Brain Institute (ICM)
NeuroPrems is a prospective, monocentric, longitudinal, not relating to a medicinal product for human use, non-randomized, non-controlled research. The study mainly aims to identify longitudinal changes and events in multimodal markers of neurodegeneration and neuroinflammation during the presymptomatic phases of neurodegenerative diseases.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1000

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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Paris, France
        • Pitié Salpetrière Hospital
        • Principal Investigator:
          • Jean-Christophe CORVOL, MD, PhD

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study will focus on subjects potentially at high risk of developing a degenerative disease, compared to a control population of healthy volunteers and relatives with no evidence of genetic mutation under study, radiologically isolated syndrome (RIS), Idiopathic rapid eye-movement (REM) sleep behavior disorder (iRBD) and abnormal elevated levels of protein ptau217.

Description

  1. Inclusion Criteria :

    1. For all participants :

      • Male or female
      • Age ≥ 18 years
      • Signed Informed consent by the subject
      • Affiliated with a social security system or beneficiary of such a regime
      • Ability to undergo an MRI exam with Gadobutrol

    2. For presymptomatic participants only :

      • Absence of a diagnosis of neurodegenerative disease. And at least one of the criteria :
      • Known carrier or relative of a patient carrying a mutation in a causal or at-risk responsible for a neurodegenerative disease
      • Isolated REM sleep behavioral disorder
      • Radiological isolated syndrome
      • Abnormal brain protein aggregates

    3. For controls only :

      • Absence of symptoms or diagnosis of neurodegenerative disease (or criteria corresponding to at risk group)

  2. Exclusion Criteria :

    • Clinical symptoms fulfilling the criteria of a neurodegenerative disease (see table in criteria section)
    • Refusal of blood draw or brain MRI
    • MRI contraindication (see criteria section)
    • Known allergy to gadoteric acid
    • Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
    • Pregnancy or breastfeeding. For women in fertile age a urine pregnancy test will be performed before the MRI.
    • Inability to understand information about the protocol
    • Person deprived of their liberty by judicial or administrative decision
    • Person under legal protection (legal guardianship, tutelage or maintenance of justice)
    • Person without any protection and unable to consent
    • Other medical, neurological, psychiatric, or social conditions that in the investigator's opinion are likely to interfere with study conduct.

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
800 presymptomatic participants
  • Visit interview
  • Neurological evaluation (NeuroPrems Scale and Self-administered REDCap questionnaires)
  • Psychological evaluation (Motivation, life trajectories and experiencies and semi-structured interview)
  • Cognition and behavior evaluation (Neuropsychological battery and Self-administered REDCap QR)
  • Imaging (MRI 3T and PET DPA-714)
  • Neurophysiology (Eye movement recording, Magnetoencephalography, Body posture and gait recording, voice and language recording)
  • Skin aging (Skin quantitative elasticity assessment)
  • Sleep (Videopolysomnography)
  • Biosampling (Blood draw, lumbar puncture, saliva sampling, skin biopsy, nasal brush and tear fluid collection)
Radiation: PET
[18F]DPA-714 will be injected intravenously as a 1 minute intravenous bolus injection and dynamic PET acquisition will last 90 min. The aim is the quantification of the neuroimmune reaction during neuroinflammation process.
Other: MRI 3T
Brain MRI will aim at providing imaging biomarkers which will allow evaluating brain structure, microstructure, iron load, myelin, neurodegeneration of the substantia nigra and locus coeruleus, functional connectivity, brain perfusion and the glymphatic system.
Other: Oculomotricity assessment
Recording eye movements in a controlled environment (requiring no specific room or area) in binocular vision at a frequency > 500Hz, while retaining infrared video footage of eye movements for high-quality clinical monitoring.
Other: Magnetoencephalography assessment
Recording brain magnetic activity using the Elekta Neuromag® TRIUX Magnetoencephalograph ; The participant will be comfortably seated in an adjustable-height chair. The device is enclosed in a shielded room isolated from external electric and magnetic fields to measure the extremely weak magnetic activities produced by the brain.
Other: Body posture and gait assessment
The acquisition of kinematic gait parameters will be achieved ; markers are positioned on the different segments of members, recognized by a camera system positioned on the walls. Neurophysiologic muscular activity of the lower limbs will also be recorded.
Other: Voice recording
Participants will be recorded during a single session at every visit upon baseline with a professional quality head mounted microphone.
Other: Video-polysomnography
Participants will complete standard sleep questionnaires before the visit and perform neurophysiological tests including cognitive tasks before and after the sleep recording.
Biological: Blood sampling, skin biopsy, excreta sampling, lumbar puncture
Experimental analyses, genetic and multi-OMIC analyses for biomarker research.
200 healthy volunteers
  • Visit interview
  • Neurological evaluation (NeuroPrems Scale and Self-administered REDCap questionnaires)
  • Psychological evaluation (Motivation, life trajectories and experiencies and semi-structured interview)
  • Cognition and behavior evaluation (Neuropsychological battery and Self-administered REDCap QR)
  • Imaging (MRI 3T and PET DPA-714)
  • Neurophysiology (Eye movement recording, Magnetoencephalography, Body posture and gait recording, voice and language recording)
  • Skin aging (Skin quantitative elasticity assessment)
  • Sleep (Videopolysomnography)
  • Biosampling (Blood draw, lumbar puncture, saliva sampling, skin biopsy, nasal brush and tear fluid collection)
Radiation: PET
[18F]DPA-714 will be injected intravenously as a 1 minute intravenous bolus injection and dynamic PET acquisition will last 90 min. The aim is the quantification of the neuroimmune reaction during neuroinflammation process.
Other: MRI 3T
Brain MRI will aim at providing imaging biomarkers which will allow evaluating brain structure, microstructure, iron load, myelin, neurodegeneration of the substantia nigra and locus coeruleus, functional connectivity, brain perfusion and the glymphatic system.
Other: Oculomotricity assessment
Recording eye movements in a controlled environment (requiring no specific room or area) in binocular vision at a frequency > 500Hz, while retaining infrared video footage of eye movements for high-quality clinical monitoring.
Other: Magnetoencephalography assessment
Recording brain magnetic activity using the Elekta Neuromag® TRIUX Magnetoencephalograph ; The participant will be comfortably seated in an adjustable-height chair. The device is enclosed in a shielded room isolated from external electric and magnetic fields to measure the extremely weak magnetic activities produced by the brain.
Other: Body posture and gait assessment
The acquisition of kinematic gait parameters will be achieved ; markers are positioned on the different segments of members, recognized by a camera system positioned on the walls. Neurophysiologic muscular activity of the lower limbs will also be recorded.
Other: Voice recording
Participants will be recorded during a single session at every visit upon baseline with a professional quality head mounted microphone.
Other: Video-polysomnography
Participants will complete standard sleep questionnaires before the visit and perform neurophysiological tests including cognitive tasks before and after the sleep recording.
Biological: Blood sampling, skin biopsy, excreta sampling, lumbar puncture
Experimental analyses, genetic and multi-OMIC analyses for biomarker research.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of change of clinical, neurophysiological, anatomical and molecular marker profiles of neurodegenerescence and neuroinflammation in presymptomatic individuals
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Clinical markers will be: neurological and neuropsychological testing, and questionnaires; Neurophysiological markers will link functional brain networks and cognitive processes by using MEG, kinematic or eye movement recordings; Anatomical markers will be: cerebral MRI, glymphatic imaging, PET and skin elasticity; Molecular markers will be: blood, CSF, skin cells, iPSC derived biomarkers, transcriptomic, proteomic and metabolomic signatures
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intra-individual change in trajectory profiles determined by multimodal analysis
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Determination by individual parameters form multimodal analysis
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Rate and mean time to symptomatic conversion/progression
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Conversion/progression defined according to international criteria for the clinical diagnosis of each disease
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Mean time of onset in genetically presymptomatic individuals
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Estimated time to onset in genetic presymptomatic individuals from the average age at diagnosis among affected family members
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Rate of change for each study marker
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Period of changes defined (1) as breakpoints in the longitudinal evolution; (2) early, intermediate or late progression for each marker in the whole cohort and for each pathological group
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Rate of change in the self-administered questionnaires
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Changes in the self-administered questionnaires on motivation, barriers and psychology
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Rate of change in consumption of information issued from Consultations, hospitalizations and medication prescriptions
Time Frame: From Year -10 to Year 10 (annual update)
Data from SNDS will be extracted during a 10-year period before and 10-year after the cohort entry. This follow-up should allow for a better understanding of when conversion occurs and to compare pathologies which involve a fairly broad spectrum of evolution.
From Year -10 to Year 10 (annual update)
Time to loss of autonomy
Time Frame: Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5
Rate of change from baseline of at least 0.1 in the utility index from EQ-5D-51
Baseline, Year 1, Year 2, Year 3, Year 4 and Year 5

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Paris Brain Institute (ICM)

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2034

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2034

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 6, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 23, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024-A00824-43

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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