Mild Cognitive ImpairmentEADPNCT04131491
Epilepsy in Alzheimer's Disease: Effect on Disease Progression
A study testing Lumbar puncture in people with Mild Cognitive Impairment and Alzheimer Disease, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
This is a long-term, prospective, interventional study to investigate the role and prevalence of subclinical epileptiform activity in the hippocampus in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease
- What is being tested?
- Lumbar puncture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteBelgium
- Study dates
- 12 Feb 2020to 30 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Cognitive concern reflecting a change in cognition reported by patient or informant or clinician
- Objective evidence of impairment in one or more cognitive domains, typically including memory.
- Preservation of independence in functional abilities
- Not demented
Who cannot join
- Age < 18 years old
- Pregnancy
- Expected death due to illness within 2 years
- Pacemaker or other ferromagnetic material that is not MRI compatible
- Other neurodegenerative or cerebrovascular disease
- Pattern compatible with Normal Pressure Hydrocephalus (NPH) (clinically, imaging)
Show all 32Show fewer
- Epilepsy
- Multiple sclerosis or other demyelinating disease
- Depression, psychosis or other mental disease
- Use of anti-epileptic drugs
- Alcohol or substance abuse
- Korsakoff syndrome
- Symptomatic liver disease
- Uncontrolled thyroid disorders
- Untreated HIV or syphilis
- Clinically significant vitamin B12 deficiency
- Severe systemic medical illness (eg end-stage cardiac disease, …)
- Healthy volunteers Inclusion criteria Age- and gender matched healthy controls
- Age < 18 years old
- Pregnancy
- Pacemaker or other ferromagnetic material that is not MRI compatible
- Mild cognitive impairment or dementia of any cause
- Epilepsy
- Multiple sclerosis or other demyelinating disease
- Depression, psychosis or other mental disease
- Use of anti-epileptic drugs
- Alcohol or substance abuse
- Symptomatic liver disease
- Uncontrolled thyroid disorders
- Untreated HIV or syphilis
- Clinically significant vitamin B12 deficiency
- Severe systemic medical illness (eg end-stage cardiac disease, …)
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
UZ Brussel
Brussels, Jette, 1090
Amber Nous, MD, 0479477937, amber.nous@live.be
About this study
This is a long-term, prospective, interventional study to investigate the role and prevalence of subclinical epileptiform activity in the hippocampus in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). The investigators would like to investigate whether subclinical epileptiform activity in the hippocampus is more prevalent in patients with MCI, compared to healthy controls and to evaluate its effects on cognitive decline. Evolution of cognitive decline will be assessed over a time period of two years.
Read the detailed description
Epilepsy is a known comorbidity of Alzheimer's disease. In the past, it was considered to be a late complication of AD. Recent literature suggest seizures to be prevalent much earlier in the time course of the disease. Systematic reviews suggest the occurrence of at least one seizure in 10-22% of AD cases and of epilepsy in 5 out of 100 AD cases. One important factor leading to the underdiagnosis of epilepsy in AD, is the fact that it is difficult to diagnose epilepsy in patients with AD because of an overlap in symptomatology (e.g. speech arrest, staring, confusion, …) A recent pilot study showed that even subclinical epileptiform discharges, without overt epilepsy, were more frequent (42%) in patients with dementia due to AD than in healthy controls (10%). These subclinical epileptic discharges were diagnosed with prolonged electroencephalogram (EEG)-monitoring and magnetoencephalogram (MEG)-registration.
There is overlap in AD and epilepsy pathogenesis. In both diseases, activation of microglia, astrogliosis, neuroinflammation and hippocampal neuronal loss has been described. Studies in mice have shown that hippocampal hyperexcitability is an early electrophysiological impairment in AD, and, that this might be a consequence of soluble Amyloid bèta oligomers. Another study in mice, expressing human Amyloid Precursor Protein (APP), showed hippocampal synchronized large amplitude potentials to be present before onset of spontaneous seizures, memory impairments or Amyloid bèta plaques. Low levels of soluble forms of Amyloid bèta might have increased excitability. Increased neuronal activity per se increases both Amyloid bèta and Tau secretion. This means that recurrent epileptic activity in AD might establish a vicious cycle.
Since hippocampal hyperactivity might be an early electrophysiological impairment in AD according to rodent studies, even before memory impairment exist, the investigators thought it to be useful to track subclinical, hippocampal epileptic activity by use of magnetoencephalogram - high density electroencephalogram (MEG-EEG) in patients with MCI due to AD (aka a stage of predementia) and compare this prevalence to healthy controls. The investigators would also like to track evolution to AD in patients with MCI and subclinical epileptiform activity versus those without.
This could support further investigations, with monitoring of the effect of several antiepileptic drugs in patients with MCI due to AD.
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Being tested
- Lumbar puncture
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lumbar punctureProcedure or surgery
Lumbar puncture for AD biomarker fluid analysis
| Study group | Role | What they receive |
|---|---|---|
| Patients with Mild Cognitive Impairment (MCI) due to AD | Other | Neuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, magnetic resonance imaging (MRI), blood sample with deep genetic profiling and Apolipoprotein E (APOE) determination. Receives: Procedure: Lumbar puncture |
| Healthy volunteers | Other | Neuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, MRI, blood sample with deep genetic profiling and APOE determination. Receives: Procedure: Lumbar puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence, expressed as percentage, of subclinical epileptiform activity in MCI due to AD patients, compared to healthy controls.
Comparison of prevalence of subclinical epileptiform activity (measured by LTM-EEG and MEG)
Measured: Patients will have their investigations at inlcusion within a time frame of 8 weeks. Healthy Volunteers will have their investigations at inclusion within a time frame of 4 weeks.
Odds ratio for conversion to clinical AD when comparing MCI patients with and without subclinical signs of epilepsy at the baseline evaluation.
Odds ratio of conversion (measured by neuropsychological examination).
Measured: Patients will have their investigations at inlcusion (time frame: 8 weeks), after 1 year (time frame: 4 weeks) and after 2 years (time frame: 4 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start12 Feb 2020
- Primary completion30 Sep 2023 (estimated)
- Study completion30 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131491
- Sponsor's protocol ID
- UZB-NEU-001
- Acronym
- EADP
- Status last verified
- May 2023
- First submitted
- 15 Oct 2019
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nous A, Seynaeve L, Feys O, Wens V, De Tiege X, Van Mierlo P, Baroumand AG, Nieboer K, Allemeersch GJ, Mangelschots S, Michiels V, van der Zee J, Van Broeckhoven C, Ribbens A, Houbrechts R, De Witte S, Wittens MMJ, Bjerke M, Vanlersberghe C, Ceyssens S, Nagels G, Smolders I, Engelborghs S. Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method. Alzheimers Res Ther. 2024 Jan 23;16(1):19. doi: 10.1186/s13195-023-01373-9.
PubMed 38263073
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epilepsy in Alzheimer's Disease: Effect on Disease Progression
- ClinicalTrials.gov ID
- NCT04131491
- Acronym / sponsor ID
- EADP / UZB-NEU-001
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- 12 Feb 2020 (actual)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 18 Oct 2019 (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.
This is a long-term, prospective, interventional study to investigate the role and prevalence of subclinical epileptiform activity in the hippocampus in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). The investigators would like to investigate whether subclinical epileptiform activity in the hippocampus is more prevalent in patients with MCI, compared to healthy controls and to evaluate its effects on cognitive decline. Evolution of cognitive decline will be assessed over a time period of two years.
Detailed description
Epilepsy is a known comorbidity of Alzheimer's disease. In the past, it was considered to be a late complication of AD. Recent literature suggest seizures to be prevalent much earlier in the time course of the disease. Systematic reviews suggest the occurrence of at least one seizure in 10-22% of AD cases and of epilepsy in 5 out of 100 AD cases. One important factor leading to the underdiagnosis of epilepsy in AD, is the fact that it is difficult to diagnose epilepsy in patients with AD because of an overlap in symptomatology (e.g. speech arrest, staring, confusion, …) A recent pilot study showed that even subclinical epileptiform discharges, without overt epilepsy, were more frequent (42%) in patients with dementia due to AD than in healthy controls (10%). These subclinical epileptic discharges were diagnosed with prolonged electroencephalogram (EEG)-monitoring and magnetoencephalogram (MEG)-registration.
There is overlap in AD and epilepsy pathogenesis. In both diseases, activation of microglia, astrogliosis, neuroinflammation and hippocampal neuronal loss has been described. Studies in mice have shown that hippocampal hyperexcitability is an early electrophysiological impairment in AD, and, that this might be a consequence of soluble Amyloid bèta oligomers. Another study in mice, expressing human Amyloid Precursor Protein (APP), showed hippocampal synchronized large amplitude potentials to be present before onset of spontaneous seizures, memory impairments or Amyloid bèta plaques. Low levels of soluble forms of Amyloid bèta might have increased excitability. Increased neuronal activity per se increases both Amyloid bèta and Tau secretion. This means that recurrent epileptic activity in AD might establish a vicious cycle.
Since hippocampal hyperactivity might be an early electrophysiological impairment in AD according to rodent studies, even before memory impairment exist, the investigators thought it to be useful to track subclinical, hippocampal epileptic activity by use of magnetoencephalogram - high density electroencephalogram (MEG-EEG) in patients with MCI due to AD (aka a stage of predementia) and compare this prevalence to healthy controls. The investigators would also like to track evolution to AD in patients with MCI and subclinical epileptiform activity versus those without.
This could support further investigations, with monitoring of the effect of several antiepileptic drugs in patients with MCI due to AD.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Mild Cognitive Impairment (MCI) due to AD | Other | Procedure: Lumbar punctureNeuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, magnetic resonance imaging (MRI), blood sample with deep genetic profiling and Apolipoprotein E (APOE) determination. |
| Healthy volunteers | Other | Procedure: Lumbar punctureNeuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, MRI, blood sample with deep genetic profiling and APOE determination. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Cognitive concern reflecting a change in cognition reported by patient or informant or clinician
- Objective evidence of impairment in one or more cognitive domains, typically including memory.
- Preservation of independence in functional abilities
- Not demented
Key exclusion criteria (32 listed)
- Age < 18 years old
- Pregnancy
- Expected death due to illness within 2 years
- Pacemaker or other ferromagnetic material that is not MRI compatible
- Other neurodegenerative or cerebrovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lumbar punctureLumbar puncture for AD biomarker fluid analysis | Procedure or surgery | Healthy volunteers, Patients with Mild Cognitive Impairment (MCI) due to AD |
Primary outcome
Prevalence, expressed as percentage, of subclinical epileptiform activity in MCI due to AD patients, compared to healthy controls.
Time frame: Patients will have their investigations at inlcusion within a time frame of 8 weeks. Healthy Volunteers will have their investigations at inclusion within a time frame of 4 weeks.
Comparison of prevalence of subclinical epileptiform activity (measured by LTM-EEG and MEG)
Odds ratio for conversion to clinical AD when comparing MCI patients with and without subclinical signs of epilepsy at the baseline evaluation.
Time frame: Patients will have their investigations at inlcusion (time frame: 8 weeks), after 1 year (time frame: 4 weeks) and after 2 years (time frame: 4 weeks).
Odds ratio of conversion (measured by neuropsychological examination).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2023.
- Derived from this study: PubMed 38263073Nous A, Seynaeve L, Feys O, Wens V, De Tiege X, Van Mierlo P, Baroumand AG, Nieboer K, Allemeersch GJ, Mangelschots S, Michiels V, van der Zee J, Van Broeckhoven C, Ribbens A, Houbrechts R, De Witte S, Wittens MMJ, Bjerke M, Vanlersberghe C, Ceyssens S, Nagels G, Smolders I, Engelborghs S. Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method. Alzheimers Res Ther. 2024 Jan 23;16(1):19. doi: 10.1186/s13195-023-01373-9.
- 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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lumbar puncture in people with Mild Cognitive Impairment and Alzheimer Disease, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
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 4 inclusion and 32 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: status not confirmed, as of the sponsor's last update on 11 May 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 Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sebastiaan Engelborghs, MD, PHD (+32 476 37 24, sebastiaan.engelborghs@uzbrussel.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence, expressed as percentage, of subclinical epileptiform activity in MCI due to AD patients, compared to healthy controls. (time frame: Patients will have their investigations at inlcusion within a time frame of 8 weeks. Healthy Volunteers will have their investigations at inclusion within a time frame of 4 weeks.). The study lists 2 primary outcomes in all. 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 NCT04131491, which also lists 1 linked publication.
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 11 May 2023.