New Imaging Biomarkers Predictive of MA Progression (MR7T-PRADA)

Identifying Imaging Biomarkers Predictive of Disability Progression in Alzheimer's Disease: Pilot Study

The pathophysiology of AD is complex. In addition to amyloid plaques and neurofibrillary degeneration, there is a metabolic alteration of the energy pathways, oxidative phosphorylation and glycolysis, which are involved in brain function. Several authors have shown a series of early metabolic dysregulations via an increase in phosphorylation at the origin of neuronal death.

Ultra-high field imaging (7T MRI) may allow, with its better spatial resolution and advanced imaging techniques, to shed light on the mechanisms of progression of Alzheimer's disease. A Magnetic Resonance Spectroscopy (MRS) examination can be coupled to brain MRI without additional risk for the patient. Multinuclear 1H-31P metabolic imaging is a promising tool that can provide information on the metabolic evolutionary profile of AD. Thus, we propose a longitudinal study in patients with early-stage AD on 7T MRI-MRS.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Magnetic Resonance Spectroscopy; Ultra High Field 7T; Progression of Disease; MR Biomarkers
• Intervention / Treatment: Other: MRI follow-up

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adrien JULIAN, Dr; Phone Number: +33 05.49.44.44.44; Email: adrien.julian@chu-poitiers.fr

Study Locations

• France
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Contact: Adrien Julian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• French-speaking patients aged 60 to 90 years,

• Patient in the context of Alzheimer's disease * for which imaging after MRI is prescribed as part of the usual diagnostic process,

  *Alzheimer's disease is diagnosed by the doctor of the memory consultation and is defined by :Evidence of a storage disorder in verbal episodic memory at LR/RI defined by a sum of LR < 17/48 and sum of RT < 40/48 +/- Impairment of executive functions possible (BREF, TMT grefex, verbal fluencies) +/- Impairment of instrumental functions possible (Grémots noun naming, Rey's figure, Mahieux's Battery).

• MMSE score ≥18,
• Written informed consent after the patient has been informed,
• Progressive decline for at least 6 months.

Exclusion Criteria:

--Partially or completely illiterate patient unable to read and write,

• Patient with an absolute contraindication to 7T MRI
• Severe psychiatric pathology not balanced,
• Non-degenerative neurological disease (stroke, multiple sclerosis ...),
• Patient with tumor or inflammatory pathology, or vascular leukopathy visualized in MRI (Fazekas score > 3)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patient with early onset Alzheimer's disease	Other: MRI follow-up; MRI follow-up for patient with early onset Alzheimer's disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify Magnetic Resonance Imaging biomarkers concentration (mmol/l) at baseline that are predictive of disability progression in individuals with Mild Alzheimer's disease as assessed by the Clinical Dementia Rating (CDR) scale	CDR scale : No dementia (CDR = 0), Uncertain disorders (CDR = 0.5), Mild disorders (CDR = 1), Moderate disorders (CDR = 2), Severe disorders (CDR = 3).	Baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between Imaging biomarkers concentration (mmol/l) and plasma metabolic parameters concentration (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12).	up of 12 months
Correlation between Imaging biomarkers concentration (mmol/l) and Urinary metabolic parameters (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12).	up of 12 months
Correlation between Imaging biomarkers concentration (mmol/l) and Enzymatic and protein parameters concentration (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12).	up of 12 months
Develop realistic mathematical models that integrate multiple parameters from all generated data to predict the progression of Alzheimer's disease, as evaluated using the Clinical Dementia Rating (CDR)	up of 12 months
Build an Artificial Intelligence (AI) algorithm to predict disability progression in individuals with Mild Alzheimer's disease, as assessed by the Clinical Dementia Rating scale	up of 12 months

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): October 2, 2027
• Study Completion (Estimated): January 15, 2028

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Disease Progression
• Other Study ID Numbers: MR7T-PRADA

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
• product manufactured in and exported from the U.S.: No