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

Alzheimer Disease Clinical Trial

— MADE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04522960
• Other study ID #: UZB-NEU-002
• Status: Recruiting
• Phase: N/A
• Start date: October 20, 2020
• Est. completion date: July 2023

Study information

• Verified date: May 2022
• Source: Universitair Ziekenhuis Brussel
• Contact: Sebastiaan Engelborghs, MD, PHD
• Phone: 02 477 64 10
• Email: sebastiaan.engelborghs[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Disease Progression

Intervention

Diagnostic Test:
• MEG+hdEEG+MRI
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

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussels	Jette

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 hours
Primary	Blood, saliva and urine melatonin correlations	Correlation between blood melatonin and urinary and salivary melatonin in the AD continuum	24 hours
Primary	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, ...	2 years
Primary	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.	8 weeks