Alzheimer Disease, Early OnsetEREMADNCT03923569
Epileptiform Activity During REM Sleep in Alzheimer's Disease
A study testing Overnight polysomnography, blood sample and high-resolution MRI scan in people with Alzheimer Disease, Early Onset, run by University Hospital, Toulouse at 1 site in France.
Trial summary
Recent clinical data showed that patients with Alzheimer Disease (AD) might present epilepsy at early stages of the disease (Cretin et al., 2016, Vossel et al., 2016). In mice models of Alzheimer disease, preclinical researchers observed an increase of epileptic events during Rapid Eye Movement (REM) sleep, which is… Read more about this study
- Who is it for?
- Ages 50 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- Overnight polysomnography, blood sample and high-resolution MRI scan
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- 29 Apr 2019to Jun 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 50 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For all participants:
- age from 50 to 90 years old
- affiliated to the French health care system
- For AD patients:
- meeting International Working Group (IWG)-2 criteria for diagnosis
- Mini-Mental State Examination (MMSE) ≥18 (Greco version)
Show all 9Show fewer
- For healthy volunteers:
- MMSE>25
- Dubois 5 words test ≥ 9
Who cannot join
- For all participants:
- Pregnancy
- people not able to give consent
- contraindication for MRI (metallic body parts, claustrophobia),
- aphasia, apraxia or agnosia
- neurological (other than AD) or any other serious disease (cancer, addiction, systemic disease)
Show all 19Show fewer
- non treated sleep apnea
- major depression or anxiety for more than 3 months (Beck>10) or psychiatric disease
- documented epilepsy
- use of neuroleptics (more than one dose per day)
- use of antiepileptics
- use of benzodiazepines at a dose superior or equal to two intakes per day
- use of antidepressants
- restless leg syndrome treated by dopaminergic agonists.
- For AD patients:
- other causes of dementia
- non-degenerative neurological lesions
- white matter hypersignals
- acute cognitive deficits
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Toulouse University Hospital
Toulouse, Occitanie, 31059
Brigitte POUZET, 33 5 61 77 91 25, brigitte.pouzet@inserm.fr
Jérémie PARIENTE, MD, PHD
About this study
Recent clinical data showed that patients with Alzheimer Disease (AD) might present epilepsy at early stages of the disease (Cretin et al., 2016, Vossel et al., 2016). In mice models of Alzheimer disease, preclinical researchers observed an increase of epileptic events during Rapid Eye Movement (REM) sleep, which is very unusual. This study aims at testing if patients with AD present an exacerbation of epileptic events during REM sleep, which could constitute an early biomarker of the disease. Investigators will evaluate the incidence of epilepsy during each sleep stage in 40 patients with early or moderate forms of AD and in 40 healthy subjects. Investigators will also look for a link between epilepsy during sleep in AD participants and memory performances, brain damage (by using MRI scans) and in the case of patients, the phenotype of the Apolipoprotein E(ApoE) gene.
Read the detailed description
Preclinical researchers discovered that the Tg2576 mouse model of Alzheimer Disease (AD) presents epileptiform activity specifically during sleep, with a prominent increase during REM-sleep. This phenotype is specific to AD mice since REM-sleep usually prevents seizures and epileptiform activity in animal models of epilepsy. Preclinical research also evidenced that this epileptic phenotype occurs at very early age in Tg2576 mice, far before the onset of cognitive impairments. Thus, it was hypothesized that patients with AD might present subclinical epileptiform events during sleep with a potential worsening during REM-sleep. If so, it could be used as a specific and early biomarker of AD. Since sleep is involved in memory consolidation processes, preclinical researchers also hypothesized that epileptiform events during sleep might participate to cognitive dysfunction in AD patients.
In order to test this hypothesis, a monocentric clinical study with a protocol consisting of three visits was designed aiming at evaluating seizures and subclinical epileptiform activity - and their consequences on memory - during sleep in 31 patients at early to moderate stages of AD and 31 matched healthy participants. During the first visit, a blood sample is collected of each patient for genetic testing of the ApoE gene before they undergo a high-resolution MRI scan. During the second visit (in the 60 days following the first one) participants first undergo a neuropsychological evaluation including visual, verbal and episodic memory tests before an overnight polysomnography. Following the overnight polysomnography, all subjects (patients and healthy participants) will be tested for the memories acquired the day before in order to evaluate sleep related memory consolidation. During the last visit, participants will fill out questionnaires aiming at evaluating pre-diagnostic lifestyle and they (and one family member if possible) will be interviewed about the presence of symptoms that might indicate an underlying epileptic syndrome for the participant. Healthy subjects will undergo the same procedures except for the blood test from which they will be exempted.
This should allow to evidence sleep related epileptic events, to precise their incidence in AD patients as well as in healthy participants, and to correlate these events to anomalies in brain structure and functional resting state connectivity (MRI) and/or sleep disturbances and/or cognitive decline.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- Overnight polysomnography, blood sample, high-resolution MRI scan, neuropsychological evaluation
- Keywords
- Alzheimer's disease, Rapid eye movement (REM) sleep, Memory consolidation, Epilepsy, MRI
- Medical subject headings
- Alzheimer Disease, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Overnight polysomnographyDiagnostic test
Overnight polysomnography with evaluation of each form of epileptiform activity during each vigilance state and memory scores at the overnight retention test
blood sampleDiagnostic test
blood sample for genetic testing of the Apolipoprotein E
high-resolution MRI scanDiagnostic test
Evaluation of anomalies in brain structure and functional resting state connectivity
neuropsychological evaluationBehavioural
neuropsychological evaluation including episodic memory tests before an overnight polysomnography
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's Disease patients group | Other | This group contains the 31 (anticipated) participants with a diagnosis of Alzheimer's disease Receives: Diagnostic Test: Overnight polysomnography; Diagnostic Test: blood sample; Diagnostic Test: high-resolution MRI scan; Behavioral: neuropsychological evaluation |
| Healthy control group | Other | This group contains the 31 (anticipated) age and sex -matched healthy controls Receives: Diagnostic Test: Overnight polysomnography; Diagnostic Test: high-resolution MRI scan; Behavioral: neuropsychological evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epileptiform activity during REM sleep
the proportion of participants from each group exhibiting a significant epileptiform activity (seizures and/or interictal spikes) during REM sleep.
. Epileptiform activity will be defined as either at least one spike, or at least 4 paroxysmal activities.
Measured: Day 2
Secondary outcomes (18)
Number of epileptiform activity according to sleep-wake cycle
Number of epileptiform activity according to sleep-wake cycle in each group
Measured: Day 2
Frequency of epileptiform activity according to sleep-wake cycle
Frequency of epileptiform activity according to sleep-wake cycle in each group
Measured: Day 2
lateralization of epileptiform activity according to sleep-wake cycle
lateralization of epileptiform activity according to sleep-wake cycle in each group
Measured: Day 2
localization of epileptiform activity according to sleep-wake cycle
localization of epileptiform activity according to sleep-wake cycle in each group
Measured: Day 2
Comparison of sleep characterization between the two groups: total sleep time
total sleep time in hours and minutes
Measured: Day 2
Comparison of sleep characterization between the two groups: number of sleep cycles
number of sleep cycles
Measured: Day 2
Comparison of sleep characterization between the two groups: time spent awake during the night
time spent awake during the night
Measured: Day 2
Comparison of sleep characterization between the two groups: index of micro-awakenings
index of micro-awakenings
Measured: Day 2
Comparison of sleep characterization between the two groups: distribution of different sleep stages in time
distribution of different sleep stages in time
Measured: Day 2
Comparison of sleep characterization between the two groups: distribution of different sleep stages in percentage
distribution of different sleep stages in percentage
Measured: Day 2
Comparison of sleep characterization between the two groups: index of periodic movements
the index of periodic movements
Measured: Day 2
Comparison of sleep characterization between the two groups: index of hypopnea
index of hypopnea (central and obstructive components)
Measured: Day 2
Comparison of memory scores at the overnight retention test between the two groups
The memory scores are combined to compute a total score
Measured: Day 2
symptoms of an underlying epileptic syndrome
The score on the questionnaire aiming at discovering potential symptoms of an underlying epileptic syndrome
Measured: Month 5
sleep spindles in different sleep stages
The number and the density of sleep spindles in different sleep stages
Measured: day 2
results of the cognitive reserve inventory (CRIq)
Correlation between the frequency of epileptiform activity, the score on the epilepsy questionnaire and the index of micro-awakenings in the different sleep stages and: the results of the cognitive reserve inventory (CRIq)
Measured: month 5
speed of cognitive decline.
Correlation between the frequency of epileptiform activity, the score on the epilepsy questionnaire and the index of micro-awakenings in the different sleep stages and: the speed of cognitive decline.
Measured: month 5
density of sleep spindles in the different sleep stages
Correlation between the frequency of epileptiform activity, the score on the epilepsy questionnaire and the index of micro-awakenings in the different sleep stages and: the density of sleep spindles in the different sleep stages
Measured: month 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2019
- Study start29 Apr 2019
- Primary completionJun 2023 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe 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
- Model description
- 2 compared groups (Alzheimer's Disease patients vs controls)
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherches sur la Cognition Animale (CRCA - UMR5169 CNRS/UPS), Centre de Recherche Cerveau & Cognition (CerCo - UMR5549 CNRS/UPS), Toulouse NeuroImaging Center (ToNIC - UMR 1214 Inserm/UPS), Fondation Plan Alzheimer, IHNPS/FHU HoPeS
- Responsible party
- Sponsor
- Investigators
- Lionel Dahan, PHD, Study director, Centre de Recherches sur la Cognition Animale (CRCA), UMR CNRS 5169
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03923569
- Sponsor's protocol ID
- RC31/18/0265
- Other IDs
- 2018-A02229-46
- Acronym
- EREMAD
- Status last verified
- Jul 2021
- First submitted
- 29 Mar 2019
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epileptiform Activity During REM Sleep in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03923569
- Acronym / sponsor ID
- EREMAD / RC31/18/0265
- Conditions
- Alzheimer Disease, Early Onset
- Keywords
- Alzheimer's disease, Rapid eye movement (REM) sleep, Memory consolidation, Epilepsy, MRI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Centre de Recherches sur la Cognition Animale (CRCA - UMR5169 CNRS/UPS), Centre de Recherche Cerveau & Cognition (CerCo - UMR5549 CNRS/UPS), Toulouse NeuroImaging Center (ToNIC - UMR 1214 Inserm/UPS), Fondation Plan Alzheimer, IHNPS/FHU HoPeS
- Study start
- 29 Apr 2019 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 22 Apr 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.
Recent clinical data showed that patients with Alzheimer Disease (AD) might present epilepsy at early stages of the disease (Cretin et al., 2016, Vossel et al., 2016). In mice models of Alzheimer disease, preclinical researchers observed an increase of epileptic events during Rapid Eye Movement (REM) sleep, which is very unusual. This study aims at testing if patients with AD present an exacerbation of epileptic events during REM sleep, which could constitute an early biomarker of the disease. Investigators will evaluate the incidence of epilepsy during each sleep stage in 40 patients with early or moderate forms of AD and in 40 healthy subjects. Investigators will also look for a link between epilepsy during sleep in AD participants and memory performances, brain damage (by using MRI scans) and in the case of patients, the phenotype of the Apolipoprotein E(ApoE) gene.
Detailed description
Preclinical researchers discovered that the Tg2576 mouse model of Alzheimer Disease (AD) presents epileptiform activity specifically during sleep, with a prominent increase during REM-sleep. This phenotype is specific to AD mice since REM-sleep usually prevents seizures and epileptiform activity in animal models of epilepsy. Preclinical research also evidenced that this epileptic phenotype occurs at very early age in Tg2576 mice, far before the onset of cognitive impairments. Thus, it was hypothesized that patients with AD might present subclinical epileptiform events during sleep with a potential worsening during REM-sleep. If so, it could be used as a specific and early biomarker of AD. Since sleep is involved in memory consolidation processes, preclinical researchers also hypothesized that epileptiform events during sleep might participate to cognitive dysfunction in AD patients.
In order to test this hypothesis, a monocentric clinical study with a protocol consisting of three visits was designed aiming at evaluating seizures and subclinical epileptiform activity - and their consequences on memory - during sleep in 31 patients at early to moderate stages of AD and 31 matched healthy participants. During the first visit, a blood sample is collected of each patient for genetic testing of the ApoE gene before they undergo a high-resolution MRI scan. During the second visit (in the 60 days following the first one) participants first undergo a neuropsychological evaluation including visual, verbal and episodic memory tests before an overnight polysomnography. Following the overnight polysomnography, all subjects (patients and healthy participants) will be tested for the memories acquired the day before in order to evaluate sleep related memory consolidation. During the last visit, participants will fill out questionnaires aiming at evaluating pre-diagnostic lifestyle and they (and one family member if possible) will be interviewed about the presence of symptoms that might indicate an underlying epileptic syndrome for the participant. Healthy subjects will undergo the same procedures except for the blood test from which they will be exempted.
This should allow to evidence sleep related epileptic events, to precise their incidence in AD patients as well as in healthy participants, and to correlate these events to anomalies in brain structure and functional resting state connectivity (MRI) and/or sleep disturbances and/or cognitive decline.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2 compared groups (Alzheimer's Disease patients vs controls)
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's Disease patients group | Other | Diagnostic Test: Overnight polysomnography, Diagnostic Test: blood sample, Diagnostic Test: high-resolution MRI scan, Behavioral: neuropsychological evaluationThis group contains the 31 (anticipated) participants with a diagnosis of Alzheimer's disease |
| Healthy control group | Other | Diagnostic Test: Overnight polysomnography, Diagnostic Test: high-resolution MRI scan, Behavioral: neuropsychological evaluationThis group contains the 31 (anticipated) age and sex -matched healthy controls |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- age from 50 to 90 years old
- affiliated to the French health care system
- meeting International Working Group (IWG)-2 criteria for diagnosis
- Mini-Mental State Examination (MMSE) ≥18 (Greco version)
- MMSE>25
Key exclusion criteria (19 listed)
- Pregnancy
- people not able to give consent
- contraindication for MRI (metallic body parts, claustrophobia),
- aphasia, apraxia or agnosia
- neurological (other than AD) or any other serious disease (cancer, addiction, systemic 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 |
|---|---|---|
| Overnight polysomnographyOvernight polysomnography with evaluation of each form of epileptiform activity during each vigilance state and memory scores at the overnight retention test | Diagnostic test | Alzheimer's Disease patients group, Healthy control group |
| blood sampleblood sample for genetic testing of the Apolipoprotein E | Diagnostic test | Alzheimer's Disease patients group |
| high-resolution MRI scanEvaluation of anomalies in brain structure and functional resting state connectivity | Diagnostic test | Alzheimer's Disease patients group, Healthy control group |
| neuropsychological evaluationneuropsychological evaluation including episodic memory tests before an overnight polysomnography | Behavioural | Alzheimer's Disease patients group, Healthy control group |
Primary outcome
Epileptiform activity during REM sleep
Time frame: Day 2
the proportion of participants from each group exhibiting a significant epileptiform activity (seizures and/or interictal spikes) during REM sleep. . Epileptiform activity will be defined as either at least one spike, or at least 4 paroxysmal activities.
18 secondary outcomes
Number of epileptiform activity according to sleep-wake cycle
Time frame: Day 2
Frequency of epileptiform activity according to sleep-wake cycle
Time frame: Day 2
lateralization of epileptiform activity according to sleep-wake cycle
Time frame: Day 2
localization of epileptiform activity according to sleep-wake cycle
Time frame: Day 2
Comparison of sleep characterization between the two groups: total sleep time
Time frame: Day 2
Comparison of sleep characterization between the two groups: number of sleep cycles
Time frame: Day 2
Comparison of sleep characterization between the two groups: time spent awake during the night
Time frame: Day 2
Comparison of sleep characterization between the two groups: index of micro-awakenings
Time frame: Day 2
Comparison of sleep characterization between the two groups: distribution of different sleep stages in time
Time frame: Day 2
Comparison of sleep characterization between the two groups: distribution of different sleep stages in percentage
Time frame: Day 2
Comparison of sleep characterization between the two groups: index of periodic movements
Time frame: Day 2
Comparison of sleep characterization between the two groups: index of hypopnea
Time frame: Day 2
Comparison of memory scores at the overnight retention test between the two groups
Time frame: Day 2
symptoms of an underlying epileptic syndrome
Time frame: Month 5
sleep spindles in different sleep stages
Time frame: day 2
results of the cognitive reserve inventory (CRIq)
Time frame: month 5
speed of cognitive decline.
Time frame: month 5
density of sleep spindles in the different sleep stages
Time frame: month 5
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
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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.
Lionel Dahan, PHD study director
Centre de Recherches sur la Cognition Animale (CRCA), UMR CNRS 5169
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Overnight polysomnography, blood sample and high-resolution MRI scan in people with Alzheimer Disease, Early Onset, run by University Hospital, Toulouse at 1 site in France.
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 9 inclusion and 19 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 28 Jul 2021. 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 France. 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 Luc Valton, MD (05-61-77-94-88 ext. 33, valton.l@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Epileptiform activity during REM sleep (time frame: Day 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2021.