Alzheimer DiseaseMADENCT04522960
Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity.
A study testing MEG+hdEEG+MRI in people with Alzheimer Disease, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial summary
This is a long-term, prospective, observational study to investigate and compare the levels and rhythm of melatonin in patients with AD dementia, mild cognitive impairment due to AD and healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- MEG+hdEEG+MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- 20 Oct 2020to Jul 2023
- Phase
- Interventional
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Dementia due to AD, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
- MCI due to AD, according to NIA-AA criteria
- Healthy controls: Age- and gender matched healthy controls
Who cannot join
- Patients (AD dementia, MCI)
- Age < 18 years old
- Pregnancy
- Expected death due to illness within 2 years
- Pacemaker or other ferrromagnetic material that is not MRI compatible
- Other neurodegenerative or cerebrovascular disease
Show all 39Show fewer
- Pattern compatible with NPH (clinically, imaging)
- Epilepsy
- Multiple sclerosis or other demyelinating disease
- Depression, psychosis or other mental disease
- Use of anti-epileptic drugs
- Alcohol or substance abuse
- Korsakoff syndrome
- Symptomatic liver disease
- Uncontrolled thyroid disorders
- Untreated HIV or syphilis
- Clinically significant vitamin B12 deficiency
- Severe systemic medical illness (eg end-stage cardiac disease, …)
- Use of melatonin, agomelatine, or other sleep medications
- Night worker
- REM sleep behavior disorder, OSAS
- Healthy controls
- Age < 18 years old
- Pregnancy
- Pacemaker or other ferromagnetic material that is not MRI compatible
- Mild cognitive impairment or dementia of any cause
- Epilepsy
- Multiple sclerosis or other demyelinating disease
- Depression, psychosis or other mental disease
- Use of anti-epileptic drugs
- Alcohol or substance abuse
- Symptomatic liver disease
- Uncontrolled thyroid disorders
- Untreated HIV or syphilis
- Clinically significant vitamin B12 deficiency
- Severe systemic medical illness (eg end-stage cardiac disease, …)
- Use of melatonin, agomelatine, or other sleep medications
- Night worker
- REM sleep behavior disorder, OSAS
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
Universitair Ziekenhuis Brussel
Brussels, Jette, 1090
Amber Nous, MD, +322 474 94 38, amber.nous@uzbrussel.be
About this study
This is a long-term, prospective, observational study to investigate and compare the levels and rhythm of melatonin in patients with AD dementia, mild cognitive impairment due to AD and healthy volunteers. The investigators would like to validate the use of salivary and urine melatonin measurements as an alternative for blood/CSF melatonin. Furthermore, the investigators would like to assess the effects of melatonin levels on cognition by correlating the levels and changes on cognitive tasks over a two year time frame. The investigators will also investigate whether these effects could be due to its anticonvulsive properties.
Read the detailed description
Melatonin production gets disrupted in AD, as shown in post-mortem pineal glands and CSF of AD patients. CSF melatonin levels are known to significantly drop in patients with Alzheimer's dementia. It is known that CSF melatonin levels are much higher than blood melatonin levels, due to melatonin secretion from the pineal recess directly into the third ventricle. It has never been investigated whether blood melatonin accurately correlates with CSF melatonin in AD, nor whether saliva or urine melatonin levels accurately reflect blood/CSF melatonin in the AD continuum. The investigators want to validate the use of blood, saliva and urine melatonin levels as alternative for CSF melatonin in the AD continuum to pave the way for further use of less invasive collection techniques (blood, saliva, urine instead of CSF) and to possibly study circadian rhythm in a less disrupting, in home environment (saliva, urine).
Furhtermore, melatonin exerts several potential anti-AD properties, including anti-inflammatory, anti-oxidant, tilting APP processing towards the non-amyloidogenic pathway, exerting positive effects on sleep and so on. In vivo studies furthermore point to anticonvulsive and antiepileptic effects of melatonin in a whole range of rodent models. Some evidence exists for a role of melatonin in prevention of epileptic seizures in humans.
The investigators want to investigate influence of melatonin on changes in cognition in a longitudinal way, and investigate influence on (sub)clinical epileptiform activity.
- Conditions
- Alzheimer Disease
- Being tested
- MEG+hdEEG+MRI
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEG+hdEEG+MRIDiagnostic test
Also called Lumbar puncture, Long-term EEG monitoring, Blood sampling, Saliva collection
We will perform several tests:
- Neuropsychological testing to evaluate evolution of cognition during our study.
- Lumbar puncture, blood sampling, saliva and urine collection to assess melatonin levels at several timepoints within these biological fluids.
- MEG+hdEEG and MRI (to project MEG information) ; LTM-EEG to detect epileptiform activity in patients and healthy controls
| Study group | Role | What they receive |
|---|---|---|
| Patients with dementia or mild cognitive impairment due to AD | Experimental | Dementia or MCI due to AD according to NIA-AA research criteria. Receives: Diagnostic Test: MEG+hdEEG+MRI |
| Healthy volunteers | Active comparator | Age-and-gender matched healthy controls. Receives: Diagnostic Test: MEG+hdEEG+MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
CSF and blood melatonin levels in patients with AD dementia, MCI due to AD and healthy volunteers
Comparison of CSF and blood melatonin levels between patients with MCI and dementia due to AD and healthy volunteers.
Measured: 24 hours
Blood, saliva and urine melatonin correlations
Correlation between blood melatonin and urinary and salivary melatonin in the AD continuum
Measured: 24 hours
Melatonin influence on cognition
Correlations between melatonin levels and cognitive performance over a 2 year time frame. This will be assessed by use of neuropsychological testing including MMSE, MoCA, RBANS, VAT, ...
Measured: 2 years
Melatonin influence on epileptiform activity
Correlations between melatonin levels and (subclinical) epileptiform activity. Over a time frame of 8 weeks patients will undergo neuropsychological testing (with MMSE, MoCA, RBANS, VAT...), LTM-EEG monitoring (during 24 hours), MEG + hdEEG.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start20 Oct 2020
- Primary completionJul 2023 (estimated)
- Study completionJul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04522960
- Sponsor's protocol ID
- UZB-NEU-002
- Acronym
- MADE
- Status last verified
- May 2022
- First submitted
- 13 Aug 2020
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity.
- ClinicalTrials.gov ID
- NCT04522960
- Acronym / sponsor ID
- MADE / UZB-NEU-002
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Jul 2023 (estimated)
- First posted
- 21 Aug 2020 (actual)
- 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.
This is a long-term, prospective, observational study to investigate and compare the levels and rhythm of melatonin in patients with AD dementia, mild cognitive impairment due to AD and healthy volunteers. The investigators would like to validate the use of salivary and urine melatonin measurements as an alternative for blood/CSF melatonin. Furthermore, the investigators would like to assess the effects of melatonin levels on cognition by correlating the levels and changes on cognitive tasks over a two year time frame. The investigators will also investigate whether these effects could be due to its anticonvulsive properties.
Detailed description
Melatonin production gets disrupted in AD, as shown in post-mortem pineal glands and CSF of AD patients. CSF melatonin levels are known to significantly drop in patients with Alzheimer's dementia. It is known that CSF melatonin levels are much higher than blood melatonin levels, due to melatonin secretion from the pineal recess directly into the third ventricle. It has never been investigated whether blood melatonin accurately correlates with CSF melatonin in AD, nor whether saliva or urine melatonin levels accurately reflect blood/CSF melatonin in the AD continuum. The investigators want to validate the use of blood, saliva and urine melatonin levels as alternative for CSF melatonin in the AD continuum to pave the way for further use of less invasive collection techniques (blood, saliva, urine instead of CSF) and to possibly study circadian rhythm in a less disrupting, in home environment (saliva, urine).
Furhtermore, melatonin exerts several potential anti-AD properties, including anti-inflammatory, anti-oxidant, tilting APP processing towards the non-amyloidogenic pathway, exerting positive effects on sleep and so on. In vivo studies furthermore point to anticonvulsive and antiepileptic effects of melatonin in a whole range of rodent models. Some evidence exists for a role of melatonin in prevention of epileptic seizures in humans.
The investigators want to investigate influence of melatonin on changes in cognition in a longitudinal way, and investigate influence on (sub)clinical epileptiform activity.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with dementia or mild cognitive impairment due to AD | Experimental | Diagnostic Test: MEG+hdEEG+MRIDementia or MCI due to AD according to NIA-AA research criteria. |
| Healthy volunteers | Active comparator | Diagnostic Test: MEG+hdEEG+MRIAge-and-gender matched healthy controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Dementia due to AD, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
- MCI due to AD, according to NIA-AA criteria
- Healthy controls: Age- and gender matched healthy controls
Key exclusion criteria (39 listed)
- Patients (AD dementia, MCI)
- Age < 18 years old
- Pregnancy
- Expected death due to illness within 2 years
- Pacemaker or other ferrromagnetic material that is not MRI compatible
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 |
|---|---|---|
| MEG+hdEEG+MRIAlso: Lumbar puncture, Long-term EEG monitoring, Blood sampling, Saliva collectionWe will perform several tests: * Neuropsychological testing to evaluate evolution of cognition during our study. * Lumbar puncture, blood sampling, saliva and urine collection to assess melatonin levels at several timepoints within these biological fluids. * MEG+hdEEG and MRI (to project MEG information) ; LTM-EEG to detect epileptiform activity in patients and healthy controls | Diagnostic test | Healthy volunteers, Patients with dementia or mild cognitive impairment due to AD |
Primary outcome
CSF and blood melatonin levels in patients with AD dementia, MCI due to AD and healthy volunteers
Time frame: 24 hours
Comparison of CSF and blood melatonin levels between patients with MCI and dementia due to AD and healthy volunteers.
Blood, saliva and urine melatonin correlations
Time frame: 24 hours
Correlation between blood melatonin and urinary and salivary melatonin in the AD continuum
Melatonin influence on cognition
Time frame: 2 years
Correlations between melatonin levels and cognitive performance over a 2 year time frame. This will be assessed by use of neuropsychological testing including MMSE, MoCA, RBANS, VAT, ...
Melatonin influence on epileptiform activity
Time frame: 8 weeks
Correlations between melatonin levels and (subclinical) epileptiform activity. Over a time frame of 8 weeks patients will undergo neuropsychological testing (with MMSE, MoCA, RBANS, VAT...), LTM-EEG monitoring (during 24 hours), MEG + hdEEG.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MEG+hdEEG+MRI in people with Alzheimer Disease, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
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 3 inclusion and 39 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 18 May 2022. 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 Belgium. 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 Sebastiaan Engelborghs, MD, PHD (02 477 64 10, sebastiaan.engelborghs@uzbrussel.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CSF and blood melatonin levels in patients with AD dementia, MCI due to AD and healthy volunteers (time frame: 24 hours). The study lists 4 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 18 May 2022.