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

NCT ID: NCT04522960

Last Updated: 2022-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-20
• Study Completion Date: 2023-07-31

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Patients with dementia or mild cognitive impairment due to AD

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

Group Type: EXPERIMENTAL

MEG+hdEEG+MRI

Intervention Type: DIAGNOSTIC_TEST

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

Healthy volunteers

Age-and-gender matched healthy controls.

Group Type: ACTIVE_COMPARATOR

MEG+hdEEG+MRI

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

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

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Lumbar puncture; Long-term EEG monitoring; Blood sampling; Saliva collection; Urine collection; Neuropsychological examination

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universitair Ziekenhuis Brussel

Brussels, Jette, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Sebastiaan Engelborghs, MD, PHD

Role: CONTACT

sebastiaan.engelborghs@uzbrussel.be

02 477 64 10

Amber Nous, MD

Role: CONTACT

amber.nous@uzbrussel.be

0479477937

Facility Contacts

Amber Nous, MD

Role: primary

amber.nous@uzbrussel.be

+322 474 94 38

Other Identifiers

UZB-NEU-002

Identifier Type: -

Identifier Source: org_study_id