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Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity (NODAL)

Primary Purpose

Alzheimer Disease, Early Onset, Parkinson Disease

Status

Not yet recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

fMRI

CONFMEM

About this trial

This is an interventional diagnostic trial for Alzheimer Disease, Early Onset focused on measuring connectome

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: For all participants: French mother tongue right-handed with a level of education equal to or higher than the Certificat d'Études Primaires (Primary School Certificate) Free of any medical or psychiatric condition likely to interfere with cognition (excluding diagnosis for patients) Affiliated with a social security scheme Having received oral and written information about the protocol and having signed a consent form to participate in this research. DCS+ group: - Meeting the diagnostic criteria for "subjective cognitive decline-plus" (Jessen criteria (Jessen et al., 2014). Alzheimer's patients "Mild Cognitive Impairment due to Alzheimer's Disease," "MCI-MA": - Meeting the diagnostic criteria for "Mild neurocognitive disorder due to Alzheimer's disease" (criteria of (Albert et al., 2011)) De novo" Parkinsonian patients, "MPdn": - Presenting with newly diagnosed ("de novo") Parkinson's disease and free of cognitive deficits (criteria of Postuma et al., 2015 (Postuma et al., 2015)) Parkinsonian patients with "Mild Cognitive Impairment, "MCI-MP": - Presenting Parkinson's disease associated with "mild neurocognitive impairment" (criteria of Litvan et al., 2012 (Litvan et al., 2012)) Exclusion Criteria: All participants (healthy volunteers and patients) Contraindications to MRI : Abdominal circumference + upper limbs sticking to the body > 200 cm; Implantable pacemaker or defibrillator; Neurosurgical clips; Cochlear implants ; Neural or peripheral stimulator; Intra-orbital or encephalic metallic foreign bodies; Endoprostheses fitted less than 4 weeks ago and osteosynthesis devices fitted less than 6 weeks ago; Claustrophobia. Pregnant or breast-feeding women; Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty. Patients only Score >2 on the modified Hachinski scale (Hachinski et al., 2012) Dementia according to McKhann criteria (McKhann et al., 2011) Sensory deficit interfering with experimental tests Healthy volunteers only - Cognitive impairment (MoCA score < 26)

Sites / Locations

CHU Rennes

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Arm Label

DCS+

TCL-MA

MPdn

TCL-MP

Healthy volunteers

Arm Description

Patient with subjective cognitive decline, prodromal condition of Alzheimer's disease

Patient with mild neurocognitive disorder linked to Alzheimer's disease

early-stage or de novo Parkinson's disease patients with no cognitive deficits

Patient with mild neurocognitive disorder linked to Parkinson's disease

Healthy volunteers

Outcomes

Primary Outcome Measures

Multimodal connectivity graph metrics across diseases

Multi-layer graph combining the functional and structural connectivity will provide an ideal framework for identifying multimodal features. The first layer corresponds to the functional connectivity where links represent the similarity between the fMRI signal from different cerebral regions (i.e. the nodes), using the cross-correlation. The second layer represents the structural connectivity where the edges are the fiber density between the nodes. Topological metrics of graph: 1/ the nodal centrality which quantifies how important a node is within a network, 2/ the betweenness defined as the ratio of the number of the shortest paths comprising the node to the total number of shortest paths in the graph, measures the hub property of the node and 3/ local efficiency which quantify the ability of a network to transmit information at the global and local level, will be compared between patients at-risk for Alzheimer's Disease, patients with Parkinson's Disease and healthy controls.

Secondary Outcome Measures

Multimodal connectivity graph metrics across stages of disease

Multi-layer graph combining the functional and structural connectivity will provide an ideal framework for identifying multimodal features. The first layer corresponds to the functional connectivity where links represent the correlation between the fMRI signal. The second layer represents the structural connectivity where the edges are the fiber density between the nodes. Topological metrics of graph: 1/ the nodal centrality which quantifies how important a node is within a network, 2/ the betweenness defined as the ratio of the number of the shortest paths comprising the node to the total number and 3/ local efficiency which quantify the ability of a network to transmit information, will be compared between patients at-risk for Alzheimer's Disease at the Subjective Cognitive Decline stage and at the Mild Cognitive Impairment stage. Similarly, patients with Parkinson's Disease without cognitive impairment and with Parkinson's Disease with Mild Cognitive will be compared.

Correlation between multimodal connectivity graph metrics and cognitive scores

Cognitive scores will include standard tasks (MOCA, Symbol Digit Modality Test - oral, Digit span, 16-items Free & Cued Selective Reminding Test, 10/36 spatial recall test, Oral Letter-Number Sequencing test, D-KEFS Color-Word Interference Test, Benton Judgment of Line Orientation, CLOX clock-drawing test, Boston Naming Test, Animal fluency) and an experimental recognition memory task. As for the latter, the scores used will be the congruency effect during study (RT in milliseconds), global recognition accuracy, and the effect of congruency on subsequent memory (difference in recognition accuracy between congruent and incongruent trials at study).

Full Information

NCT ID

NCT06080659

First Posted

September 22, 2023

Last Updated

October 5, 2023

Sponsor

Rennes University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT06080659

Brief Title

Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity

Acronym

NODAL

Official Title

Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 2023 (Anticipated)

Primary Completion Date

November 2026 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Rennes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The aim of the NODAL clinical trial is to demonstrate the feasibility of new, low-cost, non-invasive biomarkers of neurodegenerative pathologies as early Alzheimer and Parkinson, based on the estimation of the multimodal connectome.

Detailed Description

Alzheimer's (AD) and Parkinson's (PD) diseases are characterized by pre-clinical and asymptomatic phases, which can extend over decades, before progressing through different clinical stages where cognitive and/or motor symptoms appear. A major challenge for clinical neuroscience is the availability of reliable, non-invasive and inexpensive biomarkers to enable early diagnosis, be clinically relevant, and ideally contribute to prognosis and patient monitoring. Current criteria, which are essentially clinical, have a relatively low diagnostic accuracy, which is unfortunately responsible for a delay in diagnosis, whereas it has been established that early diagnosis makes it possible to postpone the loss of autonomy, open up opportunities for clinical trials for patients, and, epidemiologically speaking, ultimately reduce the prevalence of major neurocognitive disorders. Recent advances in neuroimaging techniques and connectome analysis have led to the identification of innovative biomarkers that reflect the disorganization of brain networks and are associated with clinical symptoms. After participant inclusion, the experimental visit will take place over half a day, for patients with early-stage Alzheimer's or Parkinson's disease and for healthy control volunteers. After clinical assessment, participants will undergo an MRI scan and then perform the CONFMEM experimental task. The aim of this paradigm is to identify the impact of cognitive conflict situations on recognition memory (the ability to judge whether or not a stimulus has been previously presented). The cerebral connectome will be assessed for each patient, with the aim of determining whether patterns can lead to pathology-specific markers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Early Onset, Parkinson Disease

Keywords

connectome

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

DCS+

Arm Type

Experimental

Arm Description

Patient with subjective cognitive decline, prodromal condition of Alzheimer's disease

Arm Title

TCL-MA

Arm Type

Experimental

Arm Description

Patient with mild neurocognitive disorder linked to Alzheimer's disease

Arm Title

MPdn

Arm Type

Experimental

Arm Description

early-stage or de novo Parkinson's disease patients with no cognitive deficits

Arm Title

TCL-MP

Arm Type

Experimental

Arm Description

Patient with mild neurocognitive disorder linked to Parkinson's disease

Arm Title

Healthy volunteers

Arm Type

Active Comparator

Arm Description

Healthy volunteers

Intervention Type

Diagnostic Test

Intervention Name(s)

fMRI

Intervention Description

functional MRI

Intervention Type

Diagnostic Test

Intervention Name(s)

CONFMEM

Intervention Description

The aim of this paradigm is to identify the impact of cognitive conflict situations on recognition memory (the ability to judge whether or not a stimulus has been previously presented).

Primary Outcome Measure Information:

Title

Multimodal connectivity graph metrics across diseases

Description

Time Frame

2 hours and 30 minutes

Secondary Outcome Measure Information:

Title

Multimodal connectivity graph metrics across stages of disease

Description

Multi-layer graph combining the functional and structural connectivity will provide an ideal framework for identifying multimodal features. The first layer corresponds to the functional connectivity where links represent the correlation between the fMRI signal. The second layer represents the structural connectivity where the edges are the fiber density between the nodes. Topological metrics of graph: 1/ the nodal centrality which quantifies how important a node is within a network, 2/ the betweenness defined as the ratio of the number of the shortest paths comprising the node to the total number and 3/ local efficiency which quantify the ability of a network to transmit information, will be compared between patients at-risk for Alzheimer's Disease at the Subjective Cognitive Decline stage and at the Mild Cognitive Impairment stage. Similarly, patients with Parkinson's Disease without cognitive impairment and with Parkinson's Disease with Mild Cognitive will be compared.

Time Frame

2 hours and 30 minutes

Title

Correlation between multimodal connectivity graph metrics and cognitive scores

Description

Time Frame

Up to 6 months (maximum delay between the study visit and the collection of standard tasks).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

marie-laure gervais, Phd

Phone

299282555

Ext

+33

marie-laure.gervais@chu-rennes.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Pierre-Yves JONIN, PhD

Phone

299284321

Ext

+33

pierreyves.jonin@chu-rennes.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pierre-Yves JONIN, PhD

Organizational Affiliation

CHU Rennes

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Rennes

City

Rennes

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pierre-Yves JONIN

First Name & Middle Initial & Last Name & Degree

Pierre-Yves JONIN, PhD

12. IPD Sharing Statement

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Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity

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