1. To determine the feasibility of performing a few functional magnetic resonance imaging (fMRI) tasks and clinical neurophysiological measurements in patients with mild to moderate AD.2. To validate the visual perception fMRI task in healthy…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Biomarker:
* Picture recognition task (Episodic memory) probing novelty and subsequent
memory (Maass et al., 2014, Nature Communications)
o Blood oxygen level dependent (BOLD) fMRI activity in the hippocampus and
entorhinal layers/sub-regions
o Subsequent memory performance (i.e .hit rate)
* Visual perception task probing layer specific memory processing (Meppelink et
al., 2009, Brain)
o Blood oxygen level dependent (BOLD) fMRI activity in the visual areas
* Resting state fMRI
o functional connectivity within the default mode network (DMN)
* Clinical neurophysiology
o 40 Hz Auditory steady state response * gamma oscillations
- Gamma-band intertrial phase coherence
- Gamma-band evoked power
o MMN
- MMN amplitude
- MMN latency
o P300
- P300 amplitude
- P300 latency
o Visual Evoked Potentials (VEP) based technique to measure LTP
- N75 amplitudes and latencies
- P100 amplitudes and latencies
- N135 amplitudes and latencies
Safety:
- (serious) adverse events ((S)AEs).
- Concomitant medication
Secondary outcome
N/A
Background summary
Alzheimer*s disease (AD) is characterised by a significant and progressive loss
of acetylcholine neurons in the brain, specifically cholinergic innervation to
the cortex and hippocampus is progressively lost. This is correlated with
cognitive deficits, disturbance in visual perception and neuropsychiatric (e.g.
hallucinations) symptoms. Selective acetylcholine receptor agonists and
modulators targeting type 1 and type 4 muscarinic acetylcholine receptors (M1
and M4 mAChR) are being developed as therapy for AD. Both these M1 and M4
receptors are present in the visual cortex. For the early phase development of
M1 and M4 receptor agonists, suitable biomarkers are required to measure the
drug effects.
In this study of several fMRI and EEG based measurements the feasibility to
function as a biomarker and the difference between patients with mild to
moderate AD and healthy elderly will be assessed.
Study objective
1. To determine the feasibility of performing a few functional magnetic
resonance imaging (fMRI) tasks and clinical neurophysiological measurements in
patients with mild to moderate AD.
2. To validate the visual perception fMRI task in healthy subjects.
Study design
The total duration of the study for each subject will be maximal 42 days.
* Screening: medical screening will take place within 42 days prior to inclusion
* Study day (Day 1): On this day clinical neurophysiological measurements and
the fMRI scan will be performed
* No follow-up visit is planned
Study burden and risks
During this study the participants will have 2 study visits:
-screening visit: medical screening with medical history, physical examination,
questionnaires (MMSE, GDS NPI and CDR (first in AD patients only))
study time visit:
- urine drug screening
- breath alcohol test
- One blood sample will be taken to determine APOE genotype.
- fMRI measurement
- clinical neurophysiological measurements (incl. EEG)
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Aged 50- 80 years;
2. Ability to communicate well with the investigator in the Dutch language;
3. Willing to give written informed consent and to comply with the study
restrictions;
Additional inclusion criteria for the AD subjects are:
4. Diagnosed with probable AD according to the National Institute of
Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease
and Related Disorders Association (NINCDS-ADRDA) criteria confirmed by the
treating physician;
5. MMSE score 18-26 (inclusive);
6. CDR global rating score of 0.5 or 1.0 or 2 at screening;
Additional inclusion criteria for the healthy controls are:
7. MMSE score * 27.
Exclusion criteria
1. Any contra-indications for MRI (prostheses, implants, claustrophobia,
pacemakers, etc.);
2. Presence or history of alcohol abuse, or daily alcohol consumption exceeding
2 standard drinks per day on average for females or exceeding 3 standard drinks
per day on average for males (1 standard drink = 10 grams of alcohol), or a
positive breath alcohol test at screening or upon admission to the Clinical
Research Unit (CRU);
3. Use of tobacco and/or nicotine-containing products within 30 days of day 1;
4. Positive urine drug screen at screening or day 1;
5. Unable to refrain from use of (methyl) xanthine (e.g. coffee, tea, cola,
chocolate) from 24 hours prior to day 1 until discharge from the CRU;
6. Use of concomitant medication which reduces the level of alertness;
7. Concussion or other acute head trauma in the past six months.
8. A Geriatric Depression Scale * 15 (GDS) score *6;
Exclusion criteria for AD subjects are:
9. Clinically relevant history of abnormal physical or mental health, other
than AD, interfering with the study as determined by medical history taking
obtained during the screening visit and/or at the start of day 1 as judged by
the investigator (including (but not limited to), neurological, psychiatric,
endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal
disorder).
10. Use of cholinesterase inhibitors, Memantine or herbal treatments such as
Ginkgo Biloba in patients with mild AD.
Exclusion criteria for healthy subjects:
11. Clinically relevant history of abnormal physical or mental health
interfering with the study as determined by medical history taking and physical
examinations obtained during the screening visit and/or at the start of day 1
as judged by the investigator (including (but not limited to), neurological,
psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic,
or renal disorder).
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 | NL65882.056.18 |