Cerebellar iTBS Mode Transcranial Magnetic Stimulation for the Treatment of Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

A Randomized, Controlled Clinical Study on Cerebellar iTBS Mode Transcranial Magnetic Stimulation for the Treatment of Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06379100
• Other study ID #: KY20232388
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 25, 2024
• Est. completion date: September 25, 2024

Study information

• Verified date: April 2024
• Source: Xijing Hospital
• Contact: Xin Zhang, doctor
• Phone: 13154378732
• Email: zx312316[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study the therapeutic effect and potential neural mechanisms of cerebellar iTBS mode transcranial magnetic stimulation on Alzheimer's disease patients through MRI and EEG.

Description:

This study intends to apply intermittent therapy for the first time θ The Outbreak Stimulation (iTBS) mode was used for rTMS treatment in the cerebellum of Alzheimer's disease (AD). This was a randomized, double-blind, parallel, and sham stimulation controlled clinical trial, which included 28 AD patients. All patients were randomly divided into the iTBS group and the sham stimulation group. Collect clinical information, scales, magnetic resonance imaging, TMS synchronous electroencephalography, polysomnography monitoring, etc., and then perform TMS/false stimulation treatment on subjects for 4 weeks (a total of 20 times); After treatment and one month follow-up, relevant scales, magnetic resonance imaging, TMS synchronous electroencephalogram and other data were collected again, and appropriate statistical methods were used to analyze the therapeutic effect.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 28
• Est. completion date: September 25, 2024
• Est. primary completion date: August 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subject diagnosed with early Alzheimer's disease or related diseases according to NINCDS-ACDRADA criteria.
• Age: 50-80 years old;
• The MMSE score ranges from 15 to 26, and the Clinical Dementia Rating (CDR) score is 0.5 to 1; Hamilton Depression Scale (HAM-D) score = 14 points;
• CSF biomarker evidence of Alzheimer's disease amyloid and tau pathology
• A stable dose of cholinesterase inhibitors (such as donepezil and cabalatine) for at least 6 consecutive weeks, without the need to change the dose during intervention and observation;

Exclusion Criteria:

• CDR>2
• Any history or clinical signs of other severe psychiatric illnesses (like major depression,psychosis or obsessive compulsive disorder).
• History of head injury,stroke,or other neurologic disease.
• Organic brain defects on T1 or T2 images.
• History of seizures or unexplained loss of consciousness.
• Implanted pacemaker,medication pump,vagal stimulator,deep brain stimulator.
• History of substance abuse within the last 6 months.
• Unable to cooperate in completing various inspections.

Related Conditions & MeSH terms

• Alzheimer Disease
• Electroencephalogram
• Magnetic Resonance Imaging
• Transcranial Magnetic Stimulation

Intervention

Device:
• transcranial magnetic stimulation
Intermittent Theta-Burst Transcranial Magnetic Stimulation

Locations

Country	Name	City	State
China	Xijing Hospital of Air Force Military Medical University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Beckinghausen J, Sillitoe RV. Insights into cerebellar development and connectivity. Neurosci Lett. 2019 Jan 1;688:2-13. doi: 10.1016/j.neulet.2018.05.013. Epub 2018 May 7. — View Citation

GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022 Feb;7(2):e105-e125. doi: 10.1016/S2468-2667(21)00249-8. Epub 2022 Jan 6. — View Citation

Koch G, Casula EP, Bonni S, Borghi I, Assogna M, Minei M, Pellicciari MC, Motta C, D'Acunto A, Porrazzini F, Maiella M, Ferrari C, Caltagirone C, Santarnecchi E, Bozzali M, Martorana A. Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial. Brain. 2022 Nov 21;145(11):3776-3786. doi: 10.1093/brain/awac285. — View Citation

Marvel CL, Desmond JE. Functional topography of the cerebellum in verbal working memory. Neuropsychol Rev. 2010 Sep;20(3):271-9. doi: 10.1007/s11065-010-9137-7. Epub 2010 Jun 22. — View Citation

Sabbagh M, Sadowsky C, Tousi B, Agronin ME, Alva G, Armon C, Bernick C, Keegan AP, Karantzoulis S, Baror E, Ploznik M, Pascual-Leone A. Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease. Alzheimers Dement. 2020 Apr;16(4):641-650. doi: 10.1016/j.jalz.2019.08.197. Epub 2020 Jan 16. — View Citation

Starowicz-Filip A, Chrobak AA, Moskala M, Krzyzewski RM, Kwinta B, Kwiatkowski S, Milczarek O, Rajtar-Zembaty A, Przewoznik D. The role of the cerebellum in the regulation of language functions. Psychiatr Pol. 2017 Aug 29;51(4):661-671. doi: 10.12740/PP/68547. Epub 2017 Aug 29. English, Polish. — View Citation

Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009 Jan 15;44(2):489-501. doi: 10.1016/j.neuroimage.2008.08.039. Epub 2008 Sep 16. — View Citation

Stoodley CJ, Schmahmann JD. Functional topography of the human cerebellum. Handb Clin Neurol. 2018;154:59-70. doi: 10.1016/B978-0-444-63956-1.00004-7. — View Citation

Wu C, Yang L, Feng S, Zhu L, Yang L, Liu TC, Duan R. Therapeutic non-invasive brain treatments in Alzheimer's disease: recent advances and challenges. Inflamm Regen. 2022 Oct 3;42(1):31. doi: 10.1186/s41232-022-00216-8. — View Citation

Wu X, Ji GJ, Geng Z, Wang L, Yan Y, Wu Y, Xiao G, Gao L, Wei Q, Zhou S, Wei L, Tian Y, Wang K. Accelerated intermittent theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer's disease: A randomized controlled trial. Brain Stimul. 2022 Jan-Feb;15(1):35-45. doi: 10.1016/j.brs.2021.11.007. Epub 2021 Nov 6. — View Citation

Xue T, Wu X, Chen S, Yang Y, Yan Z, Song Z, Zhang W, Zhang J, Chen Z, Wang Z. The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis. Sleep Med Rev. 2022 Feb;61:101573. doi: 10.1016/j.smrv.2021.101573. Epub 2021 Nov 26. — View Citation

Yao Q, Tang F, Wang Y, Yan Y, Dong L, Wang T, Zhu D, Tian M, Lin X, Shi J. Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: A randomized clinical trial. Brain Stimul. 2022 Jul-Aug;15(4):910-920. doi: 10.1016/j.brs.2022.06.004. Epub 2022 Jun 11. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The changes in CDR(Clinical Dementia Rating)	The changes in CDR-SB will constitute the major research outcome measure used to assess response to rTMS.There are two scoring methods for the CDR scale, namely Total Score Calculation (CDR-GS) and Sum of Six Content Calculation (CDR-SB). The scoring method used in this study is CDR-SB, with a total score of 18 points. The lower the score, the milder the symptoms	baseline, 4 weeks after start of the treatment
Secondary	The changes in MMSE(Mini Mental State Examination)	The changes in MMSE will constitute the secondary research outcome.The full name of MMSE is mini-mental state examination. The higher the score, the better. In this study, changes in MMSE scores before and after treatment were used as secondary observations.	baseline, 4 weeks and 4 weeks after treatment
Secondary	NPI (Neuropsychiatric Inventory)	The changes in NPI will constitute the secondary research outcome. The Neuropsychology Scale (NPI) evaluates 12 neuropsychiatric disorders which included 10 neuropsychiatric symptoms and 2 autonomic neurological symptoms based on the caregiver's perception of the patient's behavior and the perceived distress. The lower the score, the lighter the symptoms.	baseline, 4 weeks and 4 weeks after treatment
Secondary	ADL( Lawton-Brody Activities of Daily Living)	The changes in ADL will constitute the secondary research outcome. The ADL evaluates 20 items activities of daily living which included basic life ability and instrument use ability based on the caregiver's perception of the patient's behavior. The lower the score, the lighter the symptoms.	baseline, 4 weeks and 4 weeks after treatment
Secondary	DST (Digital Span Test; Forward and Backward)	The changes in DST will constitute the secondary research outcome. Digital span test (DST) was commonly used to evaluate attention ability and instantaneous memory ability.	baseline, 4 weeks and 4 weeks after treatment
Secondary	ADAS-cog(Alzheimer's disease assessment scale)	The changes in ADAS-cog will constitute the secondary research outcome. The lower the score, the lighter the symptoms.	baseline, 4 weeks and 4 weeks after treatment
Secondary	DMS(Delayed matching-to-sample task)	The DMS paradigm is a commonly used paradigm for studying working memory. This study, combined with EEG monitoring, can investigate the changes in the encoding, maintenance, and retrieval phases of working memory.The changes in DMS will constitute the secondary research outcome.	baseline, 4 weeks and 4 weeks after treatment
Secondary	MEP(Motor evoked potential)	MEP is a muscle motor complex potential recorded by stimulating the motor cortex in the contralateral target muscle; Check the overall synchronization and integrity of the transmission and transmission pathways of motor nerves from the cortex to the muscles.The changes in MEP will constitute the secondary research outcome.	baseline, 4 weeks and 4 weeks after treatment
Secondary	MRI measures	This study mainly applied resting blood oxygen level dependent functional magnetic resonance imaging (BOLD), arterial spin labeling (ASL), and magnetic resonance diffusion tensor imaging (DTI) techniques to evaluate the changes in functional connectivity of the cerebellar dentate nucleus in healthy subjects and patients before and after 4 weeks of TMS treatment, as well as the changes in the cerebellar cortical white matter fiber bundles one month after treatment.	baseline, 4 weeks and 4 weeks after treatment
Secondary	EEG(electroencephalogram)	Use electroencephalography to record resting state electroencephalograms before and after treatment, as well as during follow-up, as well as TMS synchronized electroencephalograms stimulated by single pulse TMS in the bilateral cerebellar dentate nucleus, and task state electroencephalograms during DMS paradigm. Analyzing changes in power spectrum, neural oscillations, and functional connectivity of EEG data before and after treatment and during follow-up	baseline, 4 weeks and 4 weeks after treatment