Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy (BIOMALEPSIE)
Primary Purpose
Epilepsy
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
profile of CSF biomarkers of AD
Sponsored by
About this trial
This is an interventional diagnostic trial for Epilepsy focused on measuring epilepsy, Alzheimer, biomarkers, predictive value
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 60 years
- Patients with newly diagnosed epilepsy according to the latest criteria of the International League against Epilepsy.
- MMSE ≥ 28/30.
- Patients with or without cognitive complaints.
- Patients whose brain MRI did not reveal significant abnormalities outside slight cortical atrophy.
- Patients in whom the lumbar puncture did not revealed abnormalities suggestive of an infectious disease or a limbic encephalitis.
- Patient with adequate visual and auditory skills, an oral and written language in French available to clinical and neuropsychological assessment.
- Patient who have given its written consent.
Exclusion Criteria:
- Previous history of epilepsy before age 60 years.
- Patient with against-indication to MRI (pacemaker, ferromagnetic clips, mechanical heart valves, intra-cochlear implants, intraocular foreign body, skin or other) or refusing MRI.
- Presence of an abnormality in brain MRI.
- Patients with diagnostic criteria for dementia of Alzheimer's disease, vascular dementia, mixed dementia or frontotemporal lobar degeneration.
- Patients with autoimmune encephalitis.
- Patients under legal protection measure
Sites / Locations
- Hospices Civils de Lyon
- CHU Gabriel- Montpied
- CHU des Alpes
- CHU Hôpital Nord
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Presence of biomarkers of AD in cerebrospinal fluid
Arm Description
Patients older than 60 years, with normal brain MRI and with normal cognitive functioning who demonstrate a profile of CSF biomarkers of AD suggestive of biological AD
Outcomes
Primary Outcome Measures
The primary endpoint was the number of patients in a population of subjects older than 60 years with new-onset epilepsy but without cognitive impairment whose profile of the CSF biomarkers of the AD is suggestive of an AD.
Secondary Outcome Measures
changes in episodic verbal memory at 2 years
Evolution of RL/RI-16 score between inclusion and 2 years of follow-up
changes in visual recognition memory at 2 years
Evolution of DMS 48 score between inclusion and 2 years of follow-up
Evolution of DO 80 score
Evolution of semantic memory at 2 years: Evolution of DO 80 score between inclusion and 2 years follow-up
Evolution of categorical influences
Evolution of semantic memory at 2 years: Evolution of categorical influences between inclusion and 2 years follow-up
Evolution of TOP 10 score
Evolution of semantic memory at 2 years: Evolution of TOP 10 score between inclusion and 2 years follow-up
Changes in monthly frequency of seizures at 2 years
Evolution of monthly frequency of seizures between inclusion and 2 years of follow-up
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02861846
Brief Title
Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy
Acronym
BIOMALEPSIE
Official Title
Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
March 16, 2023 (Actual)
Study Completion Date
March 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Beyond 60 years, the prevalence of epilepsy is estimated at approximately 1% and increases with age. In these patients, the etiology of epilepsy is unknown in 25% of cases, even up to 55% after 65 years. Although new-onset epilepsy in the elderly is associated with a vascular disease in 50% of cases, the hypothesis of an ongoing neurodegenerative process, including an Alzheimer's disease (AD), is also common. However, investigators do not have any marker that might help to identify the patients who develop epilepsy after 60 years and who might be, despite a normal cognitive functioning, already engaged in the pathophysiological process of AD.
A number of data suggest a link between the pathophysiological process of AD and epileptogenesis:
(i) a third of patients with epilepsy develops MA, (ii) the occurrence of epilepsy in AD is an aggravating factor for cognition, (iii) in animal models of AD, the relationship between neuronal hyperexcitability and amyloid deposits is bidirectional, the amyloid protein has a pro-seizure effect and the presence of epilepsy increases the amyloid deposits, (iv) in these models, the administration of an antiepileptic drug protects from deterioration of cognition, (v) the close relationship between amyloid and neuronal hyperexcitability might be mediated by the inflammatory processes associated with AD, and particularly the microglial activation which role in epileptogenesis has been shown elsewhere.
Investigators hypothesize that in a subgroup of patients who develop epilepsy after 60 years, the occurrence of epilepsy might reflect the presence of an ongoing amyloid pathology. Our goal is to identify through biomarkers of AD in the cerebrospinal fluid of patients who develop an epilepsy after 60 years with normal MRI and normal cognition those at high risk of later developing clinically defined AD.
Identifying patients with amyloid pathology which would be expressed through epilepsy before the onset of cognitive dysfunction might help to adapt both the management of seizures and of the cognitive dysfunction.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
epilepsy, Alzheimer, biomarkers, predictive value
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Presence of biomarkers of AD in cerebrospinal fluid
Arm Type
Other
Arm Description
Patients older than 60 years, with normal brain MRI and with normal cognitive functioning who demonstrate a profile of CSF biomarkers of AD suggestive of biological AD
Intervention Type
Biological
Intervention Name(s)
profile of CSF biomarkers of AD
Intervention Description
dosage of biomarker of AD
Primary Outcome Measure Information:
Title
The primary endpoint was the number of patients in a population of subjects older than 60 years with new-onset epilepsy but without cognitive impairment whose profile of the CSF biomarkers of the AD is suggestive of an AD.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
changes in episodic verbal memory at 2 years
Description
Evolution of RL/RI-16 score between inclusion and 2 years of follow-up
Time Frame
2 years
Title
changes in visual recognition memory at 2 years
Description
Evolution of DMS 48 score between inclusion and 2 years of follow-up
Time Frame
2 years
Title
Evolution of DO 80 score
Description
Evolution of semantic memory at 2 years: Evolution of DO 80 score between inclusion and 2 years follow-up
Time Frame
2 years
Title
Evolution of categorical influences
Description
Evolution of semantic memory at 2 years: Evolution of categorical influences between inclusion and 2 years follow-up
Time Frame
2 years
Title
Evolution of TOP 10 score
Description
Evolution of semantic memory at 2 years: Evolution of TOP 10 score between inclusion and 2 years follow-up
Time Frame
2 years
Title
Changes in monthly frequency of seizures at 2 years
Description
Evolution of monthly frequency of seizures between inclusion and 2 years of follow-up
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 60 years
Patients with newly diagnosed epilepsy according to the latest criteria of the International League against Epilepsy.
MMSE ≥ 28/30.
Patients with or without cognitive complaints.
Patients whose brain MRI did not reveal significant abnormalities outside slight cortical atrophy.
Patients in whom the lumbar puncture did not revealed abnormalities suggestive of an infectious disease or a limbic encephalitis.
Patient with adequate visual and auditory skills, an oral and written language in French available to clinical and neuropsychological assessment.
Patient who have given its written consent.
Exclusion Criteria:
Previous history of epilepsy before age 60 years.
Patient with against-indication to MRI (pacemaker, ferromagnetic clips, mechanical heart valves, intra-cochlear implants, intraocular foreign body, skin or other) or refusing MRI.
Presence of an abnormality in brain MRI.
Patients with diagnostic criteria for dementia of Alzheimer's disease, vascular dementia, mixed dementia or frontotemporal lobar degeneration.
Patients with autoimmune encephalitis.
Patients under legal protection measure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aurélie RICHARD-MORNAS, Doctor
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Study Director
Facility Information:
Facility Name
Hospices Civils de Lyon
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
CHU Gabriel- Montpied
City
Clermont-Ferrand
Country
France
Facility Name
CHU des Alpes
City
Grenoble
Country
France
Facility Name
CHU Hôpital Nord
City
Saint-Étienne
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy
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