Primary objectives:- To assess the differences in resting state EEG frequency spectrum analysis between patients with neurodegenerative and patients with non-neurological causes of MCI.* Power in microvolts squared of resting stage EEG for different…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
cognitive disorders
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is to compare the resting state EEG in patients with a
non-neurological and neurodegenerative etiology of their cognitive complaints.
Secondary outcome
Secondary endpoints include the assessing diagnostic accuracy of:
- composite of parameters registered by Trial@Home wearables as a proxy for
daily activity, and
- peak latency and amplitude of event related potentials
in patients with a non-neurodegenerative and neurodegenerative aetiology of
their cognitive complaints
Background summary
Cognitive impairment is an increasing problem in modern society. In 2018, an
estimated total of 270.000 people were suffering from some form of dementia in
The Netherlands. Due to increasing life expectancy, this number will likely
have doubled before 20401. Alzheimer*s disease is the most prevalent
neurodegenerative cause of dementia, comprising around two-thirds of all
patients with diagnosed dementia. Dementia is a diagnosis based on clinical
symptoms, of which memory deficit, language disorders and disorientation are
the most frequently seen. When at least 2 of 5 cognitive domains are affected
and interference with activities of daily living (ADL) is present, a diagnosis
of dementia can be made.2
However, since symptoms progress gradually over time, in the early stages of
disease patients often do not fulfil the criteria for dementia, instead
qualifying as *mild cognitive impairment* (MCI). It is in these instances that
additional testing can be required, searching for a biomarker to either confirm
or reject the suspicion of an underlying neurodegenerative condition. This is
especially helpful when the differential diagnosis includes
non-neurodegenerative causes such as mood disorders, which can be a major mimic
in the early stage of Alzheimer*s disease. Alongside imaging studies and
protein biomarkers (mainly amyloid-beta and tau protein), electrophysiological
tests such as electro-encephalography (EEG) and event-related potentials (ERP)
can be used to quantify deterioration of cerebral function.
EEG abnormalities can be disease specific in rare cases, but usually comprise
general slowing and reduced reactivity to stimuli.3 Previous studies have
assessed the value of EEG comparing patients with different types of dementia,
and probable Alzheimer*s disease with healthy controls, with moderate
diagnostic accuracy4-5. However, its value in distinguishing between
neurodegenerative disease and mood disorders in patients with MCI has not yet
been studied.
The Trial@Home platform developed by Centre for Human Drug Research (CHDR)
allows, through various devices, the collection of continuous data from
patients. A commonly used device is the Withings Steel HR smartwatch, which
monitors physical activity by measuring heart rate, step count, sleep duration
and sleep states. Another device which is helpful in collecting continuous data
is the Withings Sleep that further analyses the sleep pattern and REM state. In
addition, the platform allows remote monitoring via an Android application, the
MORE app, to unobtrusively collect data from smartphone sensors. The app
enables data collection from multiple phone sensors (e.g., location data) as
well as phone usage logs (e.g., app usage and phone call logs). The Trial@Home
platform also includes an electronic patient-reported outcome (ePRO) module,
the ePRO app, which captures data directly into the source database. Data is
stored on a secure server in a structured data scheme ensuring clear data
management processes, forming a prerequisite for comprehensive data analysis.
Study objective
Primary objectives:
- To assess the differences in resting state EEG frequency spectrum analysis
between patients with neurodegenerative and patients with non-neurological
causes of MCI.
* Power in microvolts squared of resting stage EEG for different frequencies:
* Delta (1.5 - 6.04 Hz)
* Theta (6.0 - 8.5 Hz)
* Alpha (8.5 - 12.5 Hz)
* Beta (12.5 - 30.0 Hz)
* Gamma (30.0 - 40.0 Hz)
* High-Gamma (30.0 - 90.0 Hz)
Secondary objectives:
- To assess the differences in event-related potentials between patients with
neurodegenerative patients with non-neurological causes of MCI.
* Passive Auditory Oddball:
o MMN amplitudes [µV] and latencies [ms] for each deviant
* Active Auditory Oddball:
o Reaction time [ms] and P300 amplitude [µV] and latency [ms] at Pz
* Auditory Steady State Response:
o Inter-trial phase coherence [a.u.] and evoked power [µV2] between 35 - 45 Hz
and 200 and 500ms.
* Auditory Sensory Gating:
o Amplitudes and latencies of P50, N100, and P200 peaks for both tones.
o Difference amplitudes of both tones of the P50, N100, and P200
Exploratory objectives:
- Differences in a composite of parameters registered by Trial@Home wearables
between patients with neurodegenerative and patients with non-neurological
causes of MCI
- Usability of Trial@Home wearable device for patients with MCI
• Vital signs (heart rate)
• Activity (step count, sleep duration)
• Geolocation (GPS)
• Voice recording (CHDR MORE App)
• Phone usage
• Sleep mat:
o Sleep duration
o Sleep onset
o Time to wake
o Sleep cycles (deep, light, REM phases
o Snoring duration (minutes)
• Dedicated usability questionnaire
Study design
This is a single center cross-sectional biomarker study to investigate the
differences of clinical neurophysiological tests (EEG and ERP) between
neurodegenerative and non-neurological causes in patients with MCI.
The total duration of the study for each subject will be up to 50 days divided
as follows:
* Screening: Up to 21 days before visit day 1;
* Study assessments: day 1 to 28
* Follow-up visit: day 29.
Subjects will visit the study unit at screening, on day 1 and on the follow-up
visit at approximately day 29
Study burden and risks
This is a non-interventional biomarker study. No investigational drug will be
administered. There is minimal risk when executing EEG. An electrode cap is
attached to the head of the subject with a special gel. When attaching the cap,
the scalp is rubbed a bit, which may irritate the skin and cause redness or
itchiness.
Considering the nature of the methods of data collection via smartphone
employed in this study, privacy issues are a potential concern. To prevent
unacceptable privacy incursions, we have developed the study assessments to be
as little invasive as possible. All subjects will be informed thoroughly
regarding the following:
• Data collected via the Withings study devices will be stored pseudonymized
and Withings and CHDR will be co-controllers of the data. Besides data
collected via the Withings study devices, only height, weight, age and a coded
subject number will be stored on the Withings servers. The key for this coded
subject number will be stored at CHDR only. The Withings® servers are stationed
in Ireland and are secure and General Data Protection Regulation (GDPR)
compliant. Respective responsibilities of CHDR and Withings regarding data
protection have been established in a data sharing agreement.
• Data collected via the CHDR MORE app will be stored on the CHDR Microsoft
Azure Cloud. No personal identifiable information is stored on the CHDR MORE
app or the CHDR MORE Cloud. CHDR is the controller of the data. The CHDR MORE
Cloud has been developed with a Privacy by Design approach and has been
qualified using the standard validation procedures of CHDR. Finally, access
rights to the data are handled by CHDR*s Standard Operating Procedures (SOP).
During the final study visit, patients will be instructed to delete all study
related applications from the smartphone, after which, further data collection
will not be possible.
All devices are CE marked for their intended purpose and instructions for good
care of the device will be given to the subjects to minimize any risks. There
is a possibility that subjects will experience discomfort while continuously
wearing the smartwatch. While we do not expect discomfort of a serious nature,
subjects will be informed of several possibilities to limit discomfort while
continuing their study participation (e.g., to take the watch off for 30
minutes twice per day during meals/showers or alternating arms).
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Male or female subject of >= 45 years of age at screening.
2. Cognitive disorders defined as mild cognitive impairment diagnosed by a
neurologist, suspected due to neurodegenerative disease or non-neurological
disorder (e.g. psychiatric disorders).
3. Willing and able to voluntary sign the informed consent form (ICF).
4. Willing and able to communicate with the investigator and site staff and to
comply with the study requirements and visits.
Exclusion criteria
1. Clinically significant findings as determined by medical history taking,
physical examination, ECG and vital signs, which, in the opinion of the
Investigator, does not allow study participation.
2. Any previously diagnosed dementia or other neurodegenerative disease at or
prior to screening
3. Any current, clinically significant, known neurological cause of cognitive
disorders at or prior to screening.
4. Inability to willfully sign the informed consent document, supported by an
MMSE < 24 at screening. Exceptionally, patients with an MMSE < 24 can be
included only if the rationale is clearly documented by the investigator (i.e.,
clear reasoning why/how the patient can willfully sign the ICF, despite the
MMSE score < 24), and there is an explicit non-objection to trial participation
from the treating neurologist (which should be documented).
5. Recent infection with hospital admission < 2 months prior to screening.
6. A positive urine drug test (morphine, benzodiazepines, cocaine, amphetamine,
THC, methamphetamine, MDMA) or positive alcohol breath test at screening.
7. Consume, on average, more than 8 units/day of (methyl)xanthines (e.g.
coffee, tea, cola, chocolate) and unable to abstain from (methyl)xanthines from
24h before Day 1 and Day 28 up until completion of the in-clinic measurements
on Day 1 and on Day 28.
8. History of clinical evidence of alcohol- or drug abuse.
9. Concerning concomitant medication:
a) First use of any concomitant medication within 28 days prior to Day 1, with
the exception of incidental use of paracetamol and/or NSAIDs.
b) Dose change of pre-existing concomitant medication within 28 days prior to
Day 1, with the exception of stopping medication more than 7 days or 5 times
the half-life before Day 1 (whichever is longer).
10. Participation in an investigational drug or device study (last dosing of
previous study was within 90 days prior to first dosing of this study)
11. Loss of blood >= 500 mL within 3 months before screening.
12. Does not own a smartphone on which the MORE application can be installed
(Android 7.0 or above)
13. If a woman: pregnant, or breast-feeding, or planning to become pregnant
during this study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85451.056.23 |