Alzheimer's DiseaseLOCUSNCT02363504
The Locus Coeruleus and Memory
An observational study of Alzheimer's Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The cause of Alzheimer's disease, the most common form of dementia, remains unknown. Neuropathological studies suggest that a small area in the brainstem, the locus coeruleus, might be the site of the onset of the disease. Read more about this study
- Who is it for?
- Ages 60 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- 7 Tesla MRI with memory task and non-invasive neurostimulation
- How many people
- 70 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2017to Dec 2020
- How long will I take part?
- 2 Months
- Phase
- Observational
- 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 60 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 35 healthy older individuals and 35 patients with prodromal Alzheimer's disease
Who may be able to join
- For the patients:
- diagnosis of prodromal Alzheimer's disease based on the latest research criteria (clinical assessment at the memory clinic : presence of at least a memory impairment, memory complaints expressed by the patient or informant, no problems in daily life functioning, no dementia and presence of biomarkers
- Clinical Dementia Rating score of 0.5 (
- Mini-Mental State Examination (MMSE) ≥ 23 and being mentally competent (in general, individuals with a MMSE ≥ 18 are considered mentally competent)
- Age: between 60 and 85 years old
- 50% female
Show all 17Show fewer
- Right-handedness
- Average level of education
- Informed consent before participation in the study
- For the healthy older individuals:
- Average neuropsychological test results, in accordance with normative data, corrected for age, education and gender
- No substantial memory complaints (according to the participant)
- Age: between 60 and 85 years old
- 50% female
- Right-handedness
- Average level of education
- Informed consent before participation in the study
Who cannot join
- Reduced vision
- Psychoactive medication use
- Abuse of alcohol and drugs
- Cognitive impairment due to alcohol/drug abuse or abuse of other substances
- Past or present psychiatric or neurological disorders (major depression, schizophrenia, bipolar disorder, psychotic disorder (or treatment for it), epilepsy, stroke, Parkinson's disease, multiple sclerosis, brain surgery, brain trauma, electroshock therapy, kidney dialysis, Menière's disease, brain infections)
- Major vascular disorders (e.g. stroke)
- Heart diseases or pacemakers
- Contraindications for scanning (e.g. brain surgery, cardiac pacemaker, metal implants, claustrophobia, body tattoos)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University
Maastricht
Heidi IL Jacobs, PhD
About this study
Official title: Focus on the Locus Coeruleus Network With 7 T MRI: Link to Memory (Dys)Function
The cause of Alzheimer's disease, the most common form of dementia, remains unknown. Neuropathological studies suggest that a small area in the brainstem, the locus coeruleus, might be the site of the onset of the disease. This area is the sole source of noradrenalin to the brain, a neurotransmitter involved in arousal, but also cognitive functions. Animal and pharmacological studies have hinted towards an important role of this area in memory functioning. However, these studies were hampered by the limited spatial resolution, making it hard to clearly localize the locus coeruleus in the brain. New developments in brain imaging allow now to visualize the brain with stunning precision. Furthermore, a non-invasive new stimulation method, transcutaneous vagus nerve stimulation, is believed to excite the locus coeruleus and thereby influencing neuronal networks and memory functioning.
There are three aims in this project:
- To investigate how the functional interaction between the locus coeruleus and other brain areas, in particular the medial temporal lobe areas, during memory processes (encoding, consolidation and retrieval) change with development of Alzheimer's disease.
- To investigate associations between noradrenaline, memory performance and brain functioning. The investigators aim to investigate how acute noradrenalin levels change during the different memory processes and whether or not this is beneficial for performance. Furthermore, the investigators will investigate whether this interaction between noradrenalin, memory performance and brain functioning is different healthy older individuals (n =35) or patients with prodromal Alzheimer's disease (n =35).
- To investigate the underlying neural network changes during transcutaneous vagus nerve stimulation. The investigators will focus on differences in functional connectivity between the locus coeruleus and the medial temporal lobe areas in healthy older individuals and prodromal Alzheimer's disease patients. An experimental condition will be compared with a sham condition in a pseudo-randomized cross-over design.
- Conditions
- Alzheimer's Disease
- Being tested
- 7 Tesla MRI with memory task and non-invasive neurostimulation
- Keywords
- Magnetic Resonance Imaging, Noradrenaline, locus coeruleus, memory
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
7 Tesla MRI with memory task and non-invasive neurostimulationOther
This is not an intervention, we investigate the neural mechanisms
| Study group | Role | What they receive |
|---|---|---|
| Healthy older controls | 7 Tesla MRI with memory task and non-invasive neurostimulation Receives: Other: 7 Tesla MRI with memory task and non-invasive neurostimulation | |
| Prodromal Alzheimer's disease patients | 7 Tesla MRI with memory task and non-invasive neurostimulation Receives: Other: 7 Tesla MRI with memory task and non-invasive neurostimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Oxygen Level Dependent (BOLD) response during a memory task
BOLD response contrasts during encoding and retrieval. For encoding: comparing neutral versus emotional, comparing old versus prodromal AD and the interaction emotional level by group. For retrieval: correctly remembered versus those incorrectly remembered; neutral versus emotional faces; lures, mistakes and hits. These contrasts will be investigated comparing both groups.
BOLD responses during the memory task will also be compared across sessions (sham versus stimulation) for both groups.
Consolidation: task-free, so the BOLD response in the locus coeruleus will be correlated with the BOLD response in any other voxel of the grey matter of the brain over time (seed-based resting-state analyses).
Measured: 60 minutes
Performance on the memory task
Mean reaction times and accuracy levels during encoding and retrieval for emotional and neutral face-name associations and for old and prodromal AD patients.
Mean reaction times and accuracy levels will also be compared across sessions: sham versus stimulation for both groups Mean reaction times and accuracy levels will also be correlated with BOLD responses during the memory task.
Measured: 60 minutes
Noradrenalin levels during the memory task
Noradrenalin levels will be measured 7 times: double baseline, before encoding, after encoding, before retrieval, after retrieval and follow-up.
Noradrenalin levels will be correlated with BOLD responses during the memory task.
Measured: 60 minutes
Secondary outcomes (3)
Grey matter volume of the locus coeruleus
manual measurement of the number of voxels of the locus coeruleus: to compare groups
Measured: 5 mintues
shape properties of the locus coeruleus
Correspondence of the location between triangle meshes (shape of the locus coeruleus) will be compared between groups
Measured: 5 minutes
Performance on neuropsychological tests
Total score on the mini-mental state examination, fluency test, letter-digit-substitution test, concept shifting task, stroop color word test and the word learning task will be compared across groups. For the stroop color word task and the concept shifting task we will also compare reaction times between both groups.
These scores will be correlated to the grey matter volume of the locus coeruleus and the shape properties of the locus coeruleus.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study start1 Feb 2017
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 70 participants (estimated)
- Target duration
- 2 Months
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research
- Responsible party
- Sponsor
- Investigators
- Frans Verhey, Prof, Study director, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363504
- Sponsor's protocol ID
- NL51297.068.14
- Acronym
- LOCUS
- Status last verified
- Feb 2020
- First submitted
- 4 Feb 2015
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Focus on the Locus Coeruleus Network With 7 T MRI: Link to Memory (Dys)Function
- ClinicalTrials.gov ID
- NCT02363504
- Acronym / sponsor ID
- LOCUS / NL51297.068.14
- Conditions
- Alzheimer's Disease
- Keywords
- Magnetic Resonance Imaging, Noradrenaline, locus coeruleus, memory
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 16 Feb 2015 (estimated)
- 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.
The cause of Alzheimer's disease, the most common form of dementia, remains unknown. Neuropathological studies suggest that a small area in the brainstem, the locus coeruleus, might be the site of the onset of the disease. This area is the sole source of noradrenalin to the brain, a neurotransmitter involved in arousal, but also cognitive functions. Animal and pharmacological studies have hinted towards an important role of this area in memory functioning. However, these studies were hampered by the limited spatial resolution, making it hard to clearly localize the locus coeruleus in the brain. New developments in brain imaging allow now to visualize the brain with stunning precision. Furthermore, a non-invasive new stimulation method, transcutaneous vagus nerve stimulation, is believed to excite the locus coeruleus and thereby influencing neuronal networks and memory functioning.
There are three aims in this project:
- To investigate how the functional interaction between the locus coeruleus and other brain areas, in particular the medial temporal lobe areas, during memory processes (encoding, consolidation and retrieval) change with development of Alzheimer's disease.
- To investigate associations between noradrenaline, memory performance and brain functioning. The investigators aim to investigate how acute noradrenalin levels change during the different memory processes and whether or not this is beneficial for performance. Furthermore, the investigators will investigate whether this interaction between noradrenalin, memory performance and brain functioning is different healthy older individuals (n =35) or patients with prodromal Alzheimer's disease (n =35).
- To investigate the underlying neural network changes during transcutaneous vagus nerve stimulation. The investigators will focus on differences in functional connectivity between the locus coeruleus and the medial temporal lobe areas in healthy older individuals and prodromal Alzheimer's disease patients. An experimental condition will be compared with a sham condition in a pseudo-randomized cross-over design.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 2 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy older controls | – | Other: 7 Tesla MRI with memory task and non-invasive neurostimulation7 Tesla MRI with memory task and non-invasive neurostimulation |
| Prodromal Alzheimer's disease patients | – | Other: 7 Tesla MRI with memory task and non-invasive neurostimulation7 Tesla MRI with memory task and non-invasive neurostimulation |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 35 healthy older individuals and 35 patients with prodromal Alzheimer's disease
Key inclusion criteria (17 listed)
- diagnosis of prodromal Alzheimer's disease based on the latest research criteria (clinical assessment at the memory clinic : presence of at least a memory impairment, memory complaints expressed by the patient or informant, no problems in daily life functioning, no dementia and presence of biomarkers
- Clinical Dementia Rating score of 0.5 (
- Mini-Mental State Examination (MMSE) ≥ 23 and being mentally competent (in general, individuals with a MMSE ≥ 18 are considered mentally competent)
- Age: between 60 and 85 years old
- 50% female
Key exclusion criteria (8 listed)
- Reduced vision
- Psychoactive medication use
- Abuse of alcohol and drugs
- Cognitive impairment due to alcohol/drug abuse or abuse of other substances
- Past or present psychiatric or neurological disorders (major depression, schizophrenia, bipolar disorder, psychotic disorder (or treatment for it), epilepsy, stroke, Parkinson's disease, multiple sclerosis, brain surgery, brain trauma, electroshock therapy, kidney dialysis, Menière's disease, brain infections)
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 |
|---|---|---|
| 7 Tesla MRI with memory task and non-invasive neurostimulationThis is not an intervention, we investigate the neural mechanisms | Other | Healthy older controls, Prodromal Alzheimer's disease patients |
Primary outcome
Blood Oxygen Level Dependent (BOLD) response during a memory task
Time frame: 60 minutes
BOLD response contrasts during encoding and retrieval. For encoding: comparing neutral versus emotional, comparing old versus prodromal AD and the interaction emotional level by group. For retrieval: correctly remembered versus those incorrectly remembered; neutral versus emotional faces; lures, mistakes and hits. These contrasts will be investigated comparing both groups. BOLD responses during the memory task will also be compared across sessions (sham versus stimulation) for both groups. Consolidation: task-free, so the BOLD response in the locus coeruleus will be correlated with the BOLD response in any other voxel of the grey matter of the brain over time (seed-based resting-state analyses).
Performance on the memory task
Time frame: 60 minutes
Mean reaction times and accuracy levels during encoding and retrieval for emotional and neutral face-name associations and for old and prodromal AD patients. Mean reaction times and accuracy levels will also be compared across sessions: sham versus stimulation for both groups Mean reaction times and accuracy levels will also be correlated with BOLD responses during the memory task.
Noradrenalin levels during the memory task
Time frame: 60 minutes
Noradrenalin levels will be measured 7 times: double baseline, before encoding, after encoding, before retrieval, after retrieval and follow-up. Noradrenalin levels will be correlated with BOLD responses during the memory task.
3 secondary outcomes
Grey matter volume of the locus coeruleus
Time frame: 5 mintues
shape properties of the locus coeruleus
Time frame: 5 minutes
Performance on neuropsychological tests
Time frame: 30 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
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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.
Frans Verhey, Prof study director
Maastricht University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer's Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
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 17 inclusion and 8 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 Feb 2020. 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 Netherlands. 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 Heidi Jacobs, PhD (+31433884090, h.jacobs@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Oxygen Level Dependent (BOLD) response during a memory task (time frame: 60 minutes). The study lists 3 primary outcomes in all. 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 Feb 2020.