Clinical trial NCT05977088: Prediction of Effectiveness of rTMS Application in Alzheimer's Patients
Official title: Prediction of Cognitive, Neurotrophic, Anti-Inflammatory, and Antioxidant Effectiveness of rTMS Application in Alzheimer's Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer's Disease
TMS-EEG
Anti-inflammatory-neuroprotective-antioxidant effect
Lead sponsor: Istanbul Medipol University Hospital
Sponsor class: OTHER
Collaborators: name: Bezmialem Vakif University
name: Saglik Bilimleri Universitesi
First posted: 2023-08-04
Enrollment: 40
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Since pharmacological methods are insufficient in the treatment processes of Alzheimer's disease, non-pharmacological methods such as Transcranial Magnetic Stimulation (TMS) have started to be tried as a treatment option as in other neurological and psychiatric diseases. Repeated (rTMS) offers a potential treatment pathway for neurological and psychiatric illnesses. rTMS benefit rate may vary depending on many factors such as the region where it is applied, the progression and the disease degree. The possible effects of TMS on Alzheimer's pathophysiology and modification of disease process (neuroprotective, anti-inflammatory and antioxidant) will also be revealed through blood samples taken from patients before and after treatment. These approaches also constitute the original value of our study.

Detailed description: Since pharmacological methods are insufficient in the treatment processes of Alzheimer's disease, non-pharmacological methods such as Transcranial Magnetic Stimulation (TMS) have started to be tried as a treatment option as in other neurological and psychiatric diseases. Repeated (rTMS) offers a potential treatment pathway for neurological and psychiatric illnesses. rTMS benefit rate may vary depending on many factors such as the region where it is applied, the progression and the disease degree. This study aim is to predict the benefit rate to be obtained from the treatment by using various evaluation parameters before starting rTMS treatment. The possible effects of TMS on Alzheimer's pathophysiology and modification of disease process (neuroprotective, anti-inflammatory and antioxidant) will also be revealed through blood samples taken from patients before and after treatment. These approaches also constitute the original value of our study.

In our project, 20 people will be included in the study and control groups and electroencephalography (EEG) and TMS will be used together in the study. Before rTMS treatment, resting EEG data will be taken for 5 minutes, eyes open and closed. At the end of all these procedures, rTMS treatment will be started, which will take 5 days. The treatment will consist of two sessions per day with a 20 Hz stimulating protocol, 1500 beats to right-left DLPFC, and totaly 3000 beats. EEG recordings will be taken again from all patients one week after the treatment.

Changes in the cognitive functions of Alzheimer's patients will be made through the neuropsychometric test battery taken before and after rTMS. With the analysis of neuropsychometric data, the study group will be divided into two subgroups that benefit from TMS and those who do not. In addition, EEG data obtained before and after-TMS will be compared with power spectrum, coherence, functional connectivity and graph methods in both the study and control groups, and information about the electrophysiological effects of TMS will be obtained.

Blood samples of the patients before and after rTMS will be taken and the changes in the metabolites given below will be compared: Brain Derived Neurotrophic Factor, Glial Based Neurotrophic Factor, Total Oxidant Level, Total Antioxidant Level, Oxidative Stress Index, Total Thiol, Native Thiol, Disulfide, Exosome, Inflammation Biomarkers (interleukin 1 Beta, interleukin 6, Tumor Necrosis Alpha, Interferon gamma, Nuclear factor kappa ß), Albumin Globulin ratio, Omega 6 and Omega 3. Thus, rTMS has possible neuroprotective, anti-inflammatory and antioxidant effects, consequently modifying the disease process. Additional information will be obtained about.

Eligibility criteria: Inclusion Criteria:

* Have been diagnosed with clinical Alzheimer's Disease in accordance with the NINCDS-ADRDA diagnostic criteria
* \>55 years old
* Clinical Dementia Rating Scale (CDR) score in the 1-2 range
* Not having any other disease that affects their cognitive functions
* Volunteer to participate in the study

Exclusion Criteria:

* Participant or relative does not give consent
* The patient's inability to participate in the entire study procedure (eg living in another city)
* The patient's history of head trauma with alcohol/substance abuse
* Presence of severe stroke and other neurological sequelae disease in the participant
* Presence of a metal implant on the head or having a pacemaker and contraindications for other TMS applications During the study or 1 month before, having/been receiving/receiving an investigational drug targeting Alzheimer's disease or neuromodulation treatment such as tDCS and TMS, other than standard treatment for AD symptom control such as acetylcholine esterase and memantine, with the potential to affect the study

Primary outcomes:
measure: The Mini Mental State Examination
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Neuropsychiatric Inventory
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Alzheimer's Disease Assessment Scale
timeFrame: Changes Before Treatment and 1 month after treatment
measure: ADSL
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Geriatric Depression Scale
timeFrame: Changes Before Treatment and 1 month after treatment
Secondary outcomes:
measure: Blood samples ELISA analyses
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Blood samples analyses
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Inflammatory Biomarker analyses
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Oxidative Stress Biomarker analyses
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Evaluation of Fatty Acid Profile Analysis with GC-MS
timeFrame: Changes Before Treatment and 1 month after treatment
measure: Metabolomics Analysis by Liquid Chromatography-Mass Spectrometer/Mass Spectrometer (LC-MS/MS)
timeFrame: Changes Before Treatment and 1 month after treatment
measure: EEG Power Spectrum Analysis
timeFrame: Changes Before Treatment and 1 month after treatment
measure: EEG Coherence Analysis
timeFrame: Changes Before Treatment and 1 month after treatment
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Medipol University Hospital
Study officials:
affiliation: Medipol University
name: Lutfu Hanoglu, Prof. DR. MD
role: PRINCIPAL_INVESTIGATOR
References: