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Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity. (MADE)

Primary Purpose

Alzheimer Disease

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
MEG+hdEEG+MRI
Sponsored by
Universitair Ziekenhuis Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Dementia due to AD, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
  2. MCI due to AD, according to NIA-AA criteria
  3. Healthy controls: Age- and gender matched healthy controls

Exclusion Criteria:

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
  • 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

Sites / Locations

  • Universitair Ziekenhuis BrusselRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Patients with dementia or mild cognitive impairment due to AD

Healthy volunteers

Arm Description

Dementia or MCI due to AD according to NIA-AA research criteria.

Age-and-gender matched healthy controls.

Outcomes

Primary Outcome Measures

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.
Blood, saliva and urine melatonin correlations
Correlation between blood melatonin and urinary and salivary melatonin in the AD continuum
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, ...
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.

Secondary Outcome Measures

Full Information

First Posted
August 13, 2020
Last Updated
May 17, 2022
Sponsor
Universitair Ziekenhuis Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT04522960
Brief Title
Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity.
Acronym
MADE
Official Title
Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 20, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitair Ziekenhuis Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with dementia or mild cognitive impairment due to AD
Arm Type
Experimental
Arm Description
Dementia or MCI due to AD according to NIA-AA research criteria.
Arm Title
Healthy volunteers
Arm Type
Active Comparator
Arm Description
Age-and-gender matched healthy controls.
Intervention Type
Diagnostic Test
Intervention Name(s)
MEG+hdEEG+MRI
Other Intervention Name(s)
Lumbar puncture, Long-term EEG monitoring, Blood sampling, Saliva collection, Urine collection, Neuropsychological examination
Intervention Description
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
Primary Outcome Measure Information:
Title
CSF and blood melatonin levels in patients with AD dementia, MCI due to AD and healthy volunteers
Description
Comparison of CSF and blood melatonin levels between patients with MCI and dementia due to AD and healthy volunteers.
Time Frame
24 hours
Title
Blood, saliva and urine melatonin correlations
Description
Correlation between blood melatonin and urinary and salivary melatonin in the AD continuum
Time Frame
24 hours
Title
Melatonin influence on cognition
Description
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, ...
Time Frame
2 years
Title
Melatonin influence on epileptiform activity
Description
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.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sebastiaan Engelborghs, MD, PHD
Phone
02 477 64 10
Email
sebastiaan.engelborghs@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Amber Nous, MD
Phone
0479477937
Email
amber.nous@uzbrussel.be
Facility Information:
Facility Name
Universitair Ziekenhuis Brussel
City
Brussels
State/Province
Jette
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amber Nous, MD
Phone
+322 474 94 38
Email
amber.nous@uzbrussel.be

12. IPD Sharing Statement

Plan to Share IPD
No

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Melatonin in Alzheimer's Disease: Effect on Disease Progression and Epileptiform Activity.

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