Prevalence of Epilepsy and Sleep Wake Disorders in Alzheimer Disease (PESAD)

October 12, 2023 updated by: Prof Dr W Van Paesschen, Universitaire Ziekenhuizen KU Leuven
Alzheimer disease is the most common of the neurodegenerative diseases. Epilepsy and sleep wake disorders are co-morbid conditions of Alzheimer disease. The investigators propose a prospective study using long-term EEG monitoring in combination with polysomnography to determine prevalence of epilepsy and sleep wake disorders in Alzheimer disease, and correlate these findings with clinical data, Alzheimer disease biomarkers and imaging studies (MRI and amyloid/tau-PET). In selected patients, the investigators will perform EEG studies with foramen ovale electrodes. The ultimate goal is to improve the outcome of patients with Alzheimer disease by early treatment of epilepsy and restoring sleep-wake disturbances.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Alzheimer disease is the most common of the neurodegenerative diseases. Epilepsy and sleep wake disorders are co-morbid conditions of Alzheimer disease, and there is evidence to suggest that the interactions are bidirectional. Neuronal activity promotes the production and secretion of amyloid β, which could actually drive pathogenesis early in the course of Alzheimer disease, and has been described in sleep wake disorders and epilepsy. Epileptic seizures in Alzheimer disease are often subtle, nocturnal and easily overlooked. We propose a prospective study using long-term EEG monitoring in combination with polysomnography to diagnose epilepsy and sleep wake disorders in Alzheimer disease, and correlate these findings with clinical data, Alzheimer disease biomarkers and imaging studies (MRI and amyloid/tau-PET). It is the hypothesis of the investigators that participants with Alzheimer disease and interictal spikes or specified sleep wake disorders (e.g., frequent nocturnal awakenings) during 48 hour scalp EEG and polysomnography are at risk for having hippocampal seizures, which are often clinically silent and not detected on scalp EEG. The investigators will invite 15 of these participants to undergo EEG studies with foramen ovale electrodes to determine the prevalence of these hippocampal seizures. The ultimate goal is to improve the outcome of patients with Alzheimer disease by early treatment of epilepsy and restoring sleep-wake disturbances.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • University Hospitals Leuven, department of Neurology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

53 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Participant must be able to understand the nature of the study and has the opportunity to have any questions answered. The participant has voluntarily signed the independent Review Board (IRB)/independent Ethics Committee (IEC) approved Informed Consent, prior to the conduct of any study procedures. If the participant is not fully competent, full informed consent must be obtained from a representative and assent must be obtained from the participant.

  2. Participant who meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for mild cognitive impairment or probable Alzheimer Disease, and have:

    • Clinical Dementia Rating (CDR)-Global Score of 0.5
    • A Mini-Mental State Examination (MMSE) score of 22 to 30
    • Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS-DMI) score of 85 or lower
  3. Participant has a positive amyloid Positron Emission Tomography (PET) scan.
  4. Participant has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4.
  5. Participant has an identified, reliable, study partner (e.g., family member), who has frequent contact with the participant and who will provide information as to the participant's cognitive and functional abilities.

Exclusion Criteria:

  1. Participant has evidence of any other clinically significant neurological disorder other than Alzheimer disease, including but not limited to:

    • Parkinson's disease
    • vascular dementia
    • significant cerebrovascular abnormalities
    • frontal-temporal dementia
    • Huntington's disease
    • normal pressure hydrocephalus
    • brain tumor
    • progressive supranuclear palsy
    • seizure disorder
    • subdural hematoma
    • multiple sclerosis
    • history of significant head trauma followed by persistent neurologic deficits
    • known structural brain abnormalities
    • obstructive sleep apnea syndrome treated with continuous positive airway pressure (CPAP)
  2. Participant has a screening MRI scan, interpreted by a radiologist with evidence of infection, infarction (including multiple lacunas in a critical memory structure), or other focal lesions.
  3. Participant has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-V or International Classification of Diseases (ICD)-10 criteria.
  4. Participant has a current diagnosis or history of drug or alcohol abuse (by DSM-V criteria) within 24 months prior to the study.
  5. Participant has a history or evidence of a malignancy within the 2 years prior to the study.
  6. Participant has a known history of Human Immunodeficiency Virus (HIV) infection.
  7. Participant has had surgery under general anesthesia within 3 months prior to the study.
  8. Receipt of an investigational product within a time period equal to 5 half-lives, if known, or within 6 weeks (for small molecules) or 6 months (for monoclonal antibodies or other biologics) prior the study.
  9. Participant has any history of prior receipt of active immunotherapy directed against tau or amyloid.
  10. Participant is taking anti-epileptic drugs or benzodiazepines.
  11. Participant has an abnormally low vitamin B 12 (cobalamin), abnormal thyroxine (T4) or an abnormally high thyroid stimulating hormone (TSH) that is considered clinically significant by the investigator.
  12. Subject has any visual, auditory or other impairment that in the Investigator's opinion would preclude collection of outcome measures.
  13. In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days.
  14. Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions (e.g., coronary artery bypass graft, percutaneous coronary intervention via cardiac catheterization, thrombolytic therapy), within 6 months of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Healthy control participants
Age- and gender matched healthy participant (n=30) with no cognitive problems and normal amyloid PET scan will undergo 48 hour scalp EEG and polysomnography
Diagnostic test: scalp EEG and polysomnography
48 hour 22 channel EEG with polysomnography
Active Comparator: Alzheimer disease
Participants with Alzheimer disease (n=100) will undergo 48 hour scalp EEG and polysomnography
Diagnostic test: scalp EEG and polysomnography
48 hour 22 channel EEG with polysomnography
Experimental: Alzheimer disease with high seizure risk
Selected participants with Alzheimer disease, with higher risk for silent hippocampal seizures after 48 hour scalp EEG and polysomnography (e.g. presence of interictal spikes or frequent nocturnal awakenings) (n=15) will undergo scalp EEG with foramen ovale electrodes with polysomnography
Diagnostic test: scalp EEG and polysomnography
48 hour 22 channel EEG with polysomnography
Diagnostic test: scalp EEG with foramen ovale electrodes with polysomnography
long-term scalp EEG with additional foramen ovale electrodes with polysomnography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epilepsy
Time Frame: during EEG recording
presence of epileptic activity
during EEG recording
Sleep wake disorder
Time Frame: during polysomnographic recording
presence of sleep wake disorders
during polysomnographic recording

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Investigators

  • Principal Investigator: Wim Van Paesschen, MD PhD, UZ and KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2020

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

July 24, 2018

First Submitted That Met QC Criteria

July 31, 2018

First Posted (Actual)

August 6, 2018

Study Record Updates

Last Update Posted (Actual)

October 13, 2023

Last Update Submitted That Met QC Criteria

October 12, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S61745

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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