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Epileptiform Activity During REM Sleep in Alzheimer's Disease (EREMAD)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alzheimer Disease, Early Onset | Diagnostic Test: Overnight polysomnography Diagnostic Test: blood sample Diagnostic Test: high-resolution MRI scan Behavioral: neuropsychological evaluation | Not Applicable |
Preclinical researchers discovered that Tg2576 mouse model of Alzheimer Disease (AD) present 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 researchers also evidenced that this epileptic phenotype occurs at very early age in Tg2576 mice, far before the onset of cognitive impairments. Thus, preclinical researchers hypothesized that patients with AD might present subclinical epileptiform events during sleep which might worsen during REM-sleep. If so, it could be used as a specific and early biomarker of AD. Since sleep is involved in the consolidation of memory, preclinical researchers also hypothesized that epileptiform events during sleep might participate to cognitive dysfunction in AD patients.
In order to test this hypothesis, preclinical researchers designed a monocentric clinical study aiming at evaluating seizures and subclinical epileptiform activity during sleep in 40 patients at early to moderate stages of AD and 40 matched healthy participants. A blood sample will be collected of each patient for genetic testing of the Apolipoprotein E before they undergo a high-resolution MRI scan and a neuropsychological evaluation including episodic memory tests before an overnight polysomnography. Healthy subjects will undergo the same procedures except for the blood test from which they will be exempted. Then, all subjects (patients and healthy participants) will be tested for the memories acquired before the polysomnography in order to evaluate sleep related memory consolidation.
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | 2 compared groups (Alzheimer's Disease patients vs controls) |
| Masking: | None (Open Label) |
| Primary Purpose: | Diagnostic |
| Official Title: | Epileptiform Activity During REM Sleep in Alzheimer's Disease |
| Actual Study Start Date : | April 29, 2019 |
| Estimated Primary Completion Date : | June 2022 |
| Estimated Study Completion Date : | June 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Alzheimer's Disease patients group
This group contains the 40 (anticipated) participants with a diagnosis of Alzheimer's disease
|
Diagnostic Test: Overnight polysomnography
Overnight polysomnography with evaluation of each form of epileptiform activity during each vigilance state and memory scores at the overnight retention test
Diagnostic Test: blood sample blood sample for genetic testing of the Apolipoprotein E
Diagnostic Test: high-resolution MRI scan Evaluation of anomalies in brain structure and functional resting state connectivity
Behavioral: neuropsychological evaluation neuropsychological evaluation including episodic memory tests before an overnight polysomnography
|
|
Healthy control group
This group contains the 40 (anticipated) age and sex -matched healthy controls
|
Diagnostic Test: Overnight polysomnography
Overnight polysomnography with evaluation of each form of epileptiform activity during each vigilance state and memory scores at the overnight retention test
Diagnostic Test: high-resolution MRI scan Evaluation of anomalies in brain structure and functional resting state connectivity
Behavioral: neuropsychological evaluation neuropsychological evaluation including episodic memory tests before an overnight polysomnography
|
- 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.
- Number of epileptiform activity according to sleep-wake cycle [ Time Frame: Day 2 ]Number of epileptiform activity according to sleep-wake cycle in each group
- Frequency of epileptiform activity according to sleep-wake cycle [ Time Frame: Day 2 ]Frequency of epileptiform activity according to sleep-wake cycle in each group
- lateralization of epileptiform activity according to sleep-wake cycle [ Time Frame: Day 2 ]lateralization of epileptiform activity according to sleep-wake cycle in each group
- localization of epileptiform activity according to sleep-wake cycle [ Time Frame: Day 2 ]localization of epileptiform activity according to sleep-wake cycle in each group
- Comparison of sleep characterization between the two groups: total sleep time [ Time Frame: Day 2 ]total sleep time in hours and minutes
- Comparison of sleep characterization between the two groups: number of sleep cycles [ Time Frame: Day 2 ]number of sleep cycles
- Comparison of sleep characterization between the two groups: time spent awake during the night [ Time Frame: Day 2 ]time spent awake during the night
- Comparison of sleep characterization between the two groups: index of micro-awakenings [ Time Frame: Day 2 ]index of micro-awakenings
- Comparison of sleep characterization between the two groups: distribution of different sleep stages in time [ Time Frame: Day 2 ]distribution of different sleep stages in time
- Comparison of sleep characterization between the two groups: distribution of different sleep stages in percentage [ Time Frame: Day 2 ]distribution of different sleep stages in percentage
- Comparison of sleep characterization between the two groups: index of periodic movements [ Time Frame: Day 2 ]the index of periodic movements
- Comparison of sleep characterization between the two groups: index of hypopnea [ Time Frame: Day 2 ]index of hypopnea (central and obstructive components)
- Comparison of memory scores at the overnight retention test between the two groups [ Time Frame: Day 2 ]The memory scores are combined to compute a total score
| Ages Eligible for Study: | 50 Years to 90 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
For all participants:
- age from 50 to 75 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) ≥20 (Greco version)
For healthy volunteers:
- MMSE>25
- Dubois 5 words test ≥ 9
Exclusion Criteria:
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)
- 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
| Contact: Luc Valton, MD | 05-61-77-94-88 ext 33 | valton.l@chu-toulouse.fr | |
| Contact: Lionel Dahan, PHD | 06.43.18.23.16 ext 33 | lionel.dahan@univ-tlse3.fr |
| France | |
| Toulouse University Hospital | Recruiting |
| Toulouse, Occitanie, France, 31059 | |
| Contact: Brigitte POUZET 33 5 61 77 91 25 brigitte.pouzet@inserm.fr | |
| Sub-Investigator: Jérémie PARIENTE, MD, PHD | |
| Sub-Investigator: Claire THALAMAS, MD | |
| Sub-Investigator: Fabienne CALVAS, MD | |
| Sub-Investigator: Rachel DEBS, MD | |
| Sub-Investigator: Marie DENUELLE, MD | |
| Sub-Investigator: Monique GALITZKY, MD | |
| Principal Investigator: Luc VALTON, MD | |
| Study Director: | Lionel Dahan, PHD | Centre de Recherches sur la Cognition Animale (CRCA), UMR CNRS 5169 |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | March 29, 2019 | ||||||||
| First Posted Date ICMJE | April 22, 2019 | ||||||||
| Last Update Posted Date | November 12, 2020 | ||||||||
| Actual Study Start Date ICMJE | April 29, 2019 | ||||||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
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.
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Epileptiform Activity During REM Sleep in Alzheimer's Disease | ||||||||
| Official Title ICMJE | Epileptiform Activity During REM Sleep in Alzheimer's Disease | ||||||||
| Brief 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 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 Tg2576 mouse model of Alzheimer Disease (AD) present 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 researchers also evidenced that this epileptic phenotype occurs at very early age in Tg2576 mice, far before the onset of cognitive impairments. Thus, preclinical researchers hypothesized that patients with AD might present subclinical epileptiform events during sleep which might worsen during REM-sleep. If so, it could be used as a specific and early biomarker of AD. Since sleep is involved in the consolidation of memory, preclinical researchers also hypothesized that epileptiform events during sleep might participate to cognitive dysfunction in AD patients. In order to test this hypothesis, preclinical researchers designed a monocentric clinical study aiming at evaluating seizures and subclinical epileptiform activity during sleep in 40 patients at early to moderate stages of AD and 40 matched healthy participants. A blood sample will be collected of each patient for genetic testing of the Apolipoprotein E before they undergo a high-resolution MRI scan and a neuropsychological evaluation including episodic memory tests before an overnight polysomnography. Healthy subjects will undergo the same procedures except for the blood test from which they will be exempted. Then, all subjects (patients and healthy participants) will be tested for the memories acquired before the polysomnography in order to evaluate sleep related memory consolidation. 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. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Not Applicable | ||||||||
| Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention Model Description: 2 compared groups (Alzheimer's Disease patients vs controls) Masking: None (Open Label)Primary Purpose: Diagnostic |
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| Condition ICMJE | Alzheimer Disease, Early Onset | ||||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
80 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | June 2022 | ||||||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria: For all participants:
For AD patients:
For healthy volunteers:
Exclusion Criteria: For all participants:
For AD patients:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 50 Years to 90 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | France | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03923569 | ||||||||
| Other Study ID Numbers ICMJE | RC31/18/0265 2018-A02229-46 ( Other Identifier: ID RCB ) |
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| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||||||
| Responsible Party | University Hospital, Toulouse | ||||||||
| Study Sponsor ICMJE | University Hospital, Toulouse | ||||||||
| Collaborators ICMJE |
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| Investigators ICMJE |
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| PRS Account | University Hospital, Toulouse | ||||||||
| Verification Date | November 2020 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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