pBFS Guided rTMS Treating Mild Alzheimer's Disease(AD)

Mild Alzheimer's Disease Clinical Trial

Official title:

A Prospective, Randomized, Double-blind, Controlled Trial of rTMS in the Treatment of Mild Alzheimer's Disease Guided by Personalized Brain Functional Sectors(pBFS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05872243
• Other study ID #: CPLXWAD2023
• Status: Recruiting
• Phase: N/A
• Start date: September 11, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: November 2023
• Source: Changping Laboratory
• Contact: Na Xu, Ph.D.
• Phone: +8618810069676
• Email: naxu[@]cpl.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate the effectiveness and safety of rTMS treatment under the guidance of personalized Brain Functional Sectors (pBFS) for the cognitive ability of patients with mild Alzheimer's disease.

Description:

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by memory impairment and cognitive decline. Personalized brain functional sectors (pBFS) using resting-state functional MRI scans have shown promise in precisely identifying individualized brain function networks. In this study, we aim to select tailored stimulation sites within the working memory network (WMN) or the default mode network (DMN) as intervention targets for mild AD patients using pBFS. To evaluate the effectiveness and safety of this intervention, participants will be randomized into four groups: active repetitive transcranial magnetic stimulation (rTMS) to the WMN group, active rTMS to the DMN group, and sham rTMS to either the WMN or DMN group at a ratio of 2:2:1:1. Each participant will receive 3600 pulse active or sham rTMS in each session, consisting of two 1800 pulse treatments with a 50-minute break in between. Two separate treatment sessions will be administered daily, resulting in a sum of 7200 pulses per day. The intervention will be administered for 15 continuous days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: August 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

Inclusion Criteria:

• Diagnosis of probable Alzheimer's disease (probable AD) based on the AD diagnostic criteria proposed by NIA-AA.
• Positive PET or positive cerebrospinal fluid test results for beta-amyloid (Aß).
• Elementary school education or higher.
• MMSE scores between 20 and 26 (including 20 and 26), or 18 and 26 for those with elementary school education.
• Clinical Dementia Scale (CDR) score of 1, indicating mild dementia.
• Stable medication for Alzheimer's disease for at least 3 months prior to treatment.
• Availability of a reliable caregiver who can assist and accompany the patient throughout the study.
• Voluntary participation with signed informed consent by the patient or legal guardian.

Exclusion Criteria:

• Patients who have other causes of cognitive decline apart from AD, including but not limited to vascular dementia, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, and dementia due to endocrine system lesions or deficiencies of folic acid, vitamin B12 or other causes.
• Patients with significant focal lesions seen on MRI, including more than two infarct foci larger than 2 cm in diameter, infarct foci in key areas such as the thalamus, hippocampus, internal olfactory cortex, pars oligo-cortical, angular gyrus, cortical and other subcortical gray matter nuclei.
• Patients with moderate to severe cerebral white matter degeneration ( Fazekas score of 3-6).
• Patients unable to undergo TMS treatment or MRI scan due to metallic foreign bodies, implanted electronic devices, or claustrophobia.
• Patients with a history of seizures or epilepsy syndrome, or seizures within the past 12 months.
• Patients with acute cardiovascular and cerebrovascular events within the 3 months prior to screening.
• Patients with severe cardiac, pulmonary, hepatic, renal, and other systemic diseases that cannot be controlled with conventional medications.
• Patients with malignant tumors or a life expectancy of less than 1 year due to reasons other than AD.
• History of alcohol or drug abuse.
• Having received other TMS treatments within the past three months.
• Having participated, or is currently participating in other clinical trial programs within the past three months.

Related Conditions & MeSH terms

• Alzheimer Disease
• Mild Alzheimer's Disease

Intervention

Device:
• active rTMS
Each participant will receive two 1800 pulse active rTMS in each session, with a 50-minute break in between. Participants will receive two separate sessions daily (a sum of 7200 pulses per day). The intervention will take place for 15 continuous days.
• sham rTMS
Each participant will receive two 1800 pulse sham rTMS in each session, with a 50-minute break in between. Participants will receive two separate sessions daily (a sum of 7200 pulses per day). The intervention will take place for 15 continuous days.

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Changping Laboratory	Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MoCA change	Change in Montreal Cognitive Assessment (MoCA) scores at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment (15 days), follow-up (90 days)
Other	NPI change	Change in Neuropsychiatric Inventory scores at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment (15 days), follow-up (90 days)
Other	AVLT change	Change in Auditory Verbal Learning Test (AVLT) at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment (15 days), follow-up (90 days)
Other	TMT change	Change in Trail Making Test (TMT)at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment (15 days), follow-up (90 days)
Other	Digit span change	Change in Digit span at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment (15 days), follow-up (90 days)
Primary	Post-treatment ADAS-Cog change	The Cognitive Subscale score change of the Alzheimer's Disease Assessment Scale, from baseline to post-treatment.	Pretreatment (baseline), Post-treatment (15 days)
Secondary	Follow-up ADAS-Cog change	The Cognitive Subscale score change of the Alzheimer's Disease Assessment Scale, from baseline to follow-up	Pretreatment(baseline), follow-up (90 days)
Secondary	MMSE change	Change in Mini-Mental State Examination (MMSE) scores at post-treatment (15 days) and follow-up (90 days) compared to baseline assessment (0 days).	Pretreatment(baseline), post-treatment(15 days), follow-up (90 days)