Advantage of Cerebellar Transcranial Magnetic Stimulation in Alzheimer's Diseases （ACT-AD）

NCT06669182 | Recruiting DMC

• 1 other identifier: KY20242285jiangwen
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

Alzheimer's Disease (AD) is the primary cause of dementia, with its prominent feature being cognitive decline. The cerebellum plays a crucial role in cognitive processing, making it a potential target for therapeutic intervention. This study will be conducted to evaluate the efficacy and safety of cerebellar Intermittent theta-burst stimulation (CRB-iTBS) in participants with mild Alzheimer's disease on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 3 months of treatment in the Core Study. This project aims to provide a valid treatment to improve the cognitive function and quality of life for those with Alzheimer's disease.

Conditions

Alzheimer Disease; Transcranial Magnetic Stimulation; Cerebellum

Keywords

Transcranial magnetic stimulation; Intermittent theta burst stimulation; Cerebellar cognitive reserve; Default mode network; Alzheimer's disease

Outcome Measures

Primary Outcomes (1)

• The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）

  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, 12 weeks after start of the treatment

Secondary Outcomes (5)

• The changes in MMSE（Mini Mental State Examination）

  baseline, 12 weeks ,24 weeks and 36 weeks after start of the treatment

• The changes in ADCS-ADL（Alzheimer's Disease Cooperative Study - Activities of Daily Living）

  baseline, 12 weeks, 24 weeks and 36 weeks after start of the treatment

• The changes in NPI（Neuropsychiatric Inventory）

  baseline, 12 weeks, 24 weeks and 36 weeks after treatment

• The changes in MRI（Magnetic Resonance Imaging）

  baseline and 12 weeks after treatment

• The changes in CDR-SB（Clinical Dementia Rating-Sum of Boxes）

  24 weeks and 36 weeks after start of the treatment

Study Arms (2)

Arms

ACTIVE COMPARATOR

Participants will receive iTBS-TMS once a day for 4 weeks, followed by once a week for 8 weeks.

Device: Intermittent Theta-Burst Transcranial Magnetic Stimulation

Assigned Interventions

SHAM COMPARATOR

Participants will receive sham iTBS-TMS once a day for 4 weeks, followed by once a week for 8 weeks.

Device: Intermittent Theta-Burst Transcranial Magnetic Stimulation

Interventions

Intermittent Theta-Burst Transcranial Magnetic Stimulation DEVICE

50Hz, stimulation intensity of 100% RMT, duration of 40s as a group of stimulation, 600 stimulation pulses, repeated stimulation of bilateral cerebellar dentate nuclei, with a 5-minute interval between each group, 1200 stimulation pulses per site, 5 times a week, treatment for 4 weeks, then treat once a week for 8 weeks.

Arms; Assigned Interventions

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 50-85 years old
• Meet the core clinical criteria of NIA-AA for possible Alzheimer's disease dementia, and PET or cerebrospinal fluid markers show elevated p-tau and decreased A β (1-42)
• MMSE score ranges from 18-26 points; CDR score 0.5-1 points
• The patient has received treatment with acetylcholinesterase inhibitors (AChEI), NMDA receptor antagonists, or mannequine therapy, and the current dosing regimen has remained stable for the 12 weeks prior to baseline assessment
• At least one adult caregiver
• The patient or legal guardian voluntarily signs the informed consent form

You may not qualify if:

• Neurodegenerative disorders other than AD.
• Significant intracranial focal or vascular pathology seen on brain MRI scan
• History of seizure (with the exception of febrile seizures in childhood)
• Any of the following psychotic disorders (DSM IV-TR criteria):
• Major depressive disorder (current)
• Schizophrenia
• Other psychotic disorders, bipolar disorder, or substance related disorders (within the past 5 years)
• GDS score ≥ 8 points in baseline assessment
• Cerebrovascular disease, severe infection, malignant tumor, or severe dysfunction of organs such as heart, liver, and kidney.
• Pregnant or lactating women
• Contraindications for TMS or MRI, metal or implanted devices in the body (such as pacemakers, deep brain stimulators).
• Participate in AD related clinical trials within 6 months prior to research registration

Sponsors & Collaborators

• Xijing Hospital: lead
• Tang-Du Hospital: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Xi'an No.3 Hospital: collaborator

Study Sites (4)

Xijing Hospital of Air Force Military Medical University

Xi'an, Shaanxi, 710032, China

RECRUITING

Tangdu Hospital of Air Force Military Medical University

Xi'an, Shannxi, China

RECRUITING

The First Affiliated Hospital of Xi'an Medical University

Xi'an, Shannxi, China

RECRUITING

The Third Hospital of Xi'an

Xi'an, Shannxi, China

RECRUITING

Related Publications (19)

• Cooperrider J, Furmaga H, Plow E, Park HJ, Chen Z, Kidd G, Baker KB, Gale JT, Machado AG. Chronic deep cerebellar stimulation promotes long-term potentiation, microstructural plasticity, and reorganization of perilesional cortical representation in a rodent model. J Neurosci. 2014 Jul 2;34(27):9040-50. doi: 10.1523/JNEUROSCI.0953-14.2014.

  PMID: 24990924 RESULT

• Pezzetta R, Gambarota F, Tarantino V, Devita M, Cattaneo Z, Arcara G, Mapelli D, Masina F. A meta-analysis of non-invasive brain stimulation (NIBS) effects on cerebellar-associated cognitive processes. Neurosci Biobehav Rev. 2024 Feb;157:105509. doi: 10.1016/j.neubiorev.2023.105509. Epub 2023 Dec 13.

  PMID: 38101590 RESULT

• Chan HH, Hogue O, Mathews ND, Hunter JG, Kundalia R, Hermann JK, Floden DP, Machado AG, Baker KB. Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent. Exp Neurol. 2022 Sep;355:114136. doi: 10.1016/j.expneurol.2022.114136. Epub 2022 Jun 3.

  PMID: 35667396 RESULT

• Olivito G, Serra L, Marra C, Di Domenico C, Caltagirone C, Toniolo S, Cercignani M, Leggio M, Bozzali M. Cerebellar dentate nucleus functional connectivity with cerebral cortex in Alzheimer's disease and memory: a seed-based approach. Neurobiol Aging. 2020 May;89:32-40. doi: 10.1016/j.neurobiolaging.2019.10.026. Epub 2020 Jan 15.

  PMID: 32081466 RESULT

• Tacyildiz AE, Bilgin B, Gungor A, Ucer M, Karadag A, Tanriover N. Dentate Nucleus: Connectivity-Based Anatomic Parcellation Based on Superior Cerebellar Peduncle Projections. World Neurosurg. 2021 Aug;152:e408-e428. doi: 10.1016/j.wneu.2021.05.102. Epub 2021 May 29.

  PMID: 34062299 RESULT

• Benarroch E. What Is the Role of the Dentate Nucleus in Normal and Abnormal Cerebellar Function? Neurology. 2024 Aug 13;103(3):e209636. doi: 10.1212/WNL.0000000000209636. Epub 2024 Jul 2. No abstract available.

  PMID: 38954796 RESULT

• Di Nuzzo C, Ruggiero F, Cortese F, Cova I, Priori A, Ferrucci R. Non-invasive Cerebellar Stimulation in Cerebellar Disorders. CNS Neurol Disord Drug Targets. 2018;17(3):193-198. doi: 10.2174/1871527317666180404113444.

  PMID: 29623859 RESULT

• van Dun K, Mitoma H, Manto M. Cerebellar Cortex as a Therapeutic Target for Neurostimulation. Cerebellum. 2018 Dec;17(6):777-787. doi: 10.1007/s12311-018-0976-8.

  PMID: 30276522 RESULT

• Manto M, Kakei S, Mitoma H. The critical need to develop tools assessing cerebellar reserve for the delivery and assessment of non-invasive cerebellar stimulation. Cerebellum Ataxias. 2021 Jan 4;8(1):2. doi: 10.1186/s40673-020-00126-w.

  PMID: 33397496 RESULT

• Arleo A, Bares M, Bernard JA, Bogoian HR, Bruchhage MMK, Bryant P, Carlson ES, Chan CCH, Chen LK, Chung CP, Dotson VM, Filip P, Guell X, Habas C, Jacobs HIL, Kakei S, Lee TMC, Leggio M, Misiura M, Mitoma H, Olivito G, Ramanoel S, Rezaee Z, Samstag CL, Schmahmann JD, Sekiyama K, Wong CHY, Yamashita M, Manto M. Consensus Paper: Cerebellum and Ageing. Cerebellum. 2024 Apr;23(2):802-832. doi: 10.1007/s12311-023-01577-7. Epub 2023 Jul 10.

  PMID: 37428408 RESULT

• Jacobs HIL, Hopkins DA, Mayrhofer HC, Bruner E, van Leeuwen FW, Raaijmakers W, Schmahmann JD. The cerebellum in Alzheimer's disease: evaluating its role in cognitive decline. Brain. 2018 Jan 1;141(1):37-47. doi: 10.1093/brain/awx194.

  PMID: 29053771 RESULT

• Liang KJ, Carlson ES. Resistance, vulnerability and resilience: A review of the cognitive cerebellum in aging and neurodegenerative diseases. Neurobiol Learn Mem. 2020 Apr;170:106981. doi: 10.1016/j.nlm.2019.01.004. Epub 2019 Jan 7.

  PMID: 30630042 RESULT

• Thal DR, Rub U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002 Jun 25;58(12):1791-800. doi: 10.1212/wnl.58.12.1791.

  PMID: 12084879 RESULT

• Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ, Castellani RJ, Crain BJ, Davies P, Del Tredici K, Duyckaerts C, Frosch MP, Haroutunian V, Hof PR, Hulette CM, Hyman BT, Iwatsubo T, Jellinger KA, Jicha GA, Kovari E, Kukull WA, Leverenz JB, Love S, Mackenzie IR, Mann DM, Masliah E, McKee AC, Montine TJ, Morris JC, Schneider JA, Sonnen JA, Thal DR, Trojanowski JQ, Troncoso JC, Wisniewski T, Woltjer RL, Beach TG. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol. 2012 May;71(5):362-81. doi: 10.1097/NEN.0b013e31825018f7.

  PMID: 22487856 RESULT

• Long JM, Holtzman DM. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell. 2019 Oct 3;179(2):312-339. doi: 10.1016/j.cell.2019.09.001. Epub 2019 Sep 26.

  PMID: 31564456 RESULT

• Sun Z, Zhang X, So KF, Jiang W, Chiu K. Targeting Microglia in Alzheimer's Disease: Pathogenesis and Potential Therapeutic Strategies. Biomolecules. 2024 Jul 11;14(7):833. doi: 10.3390/biom14070833.

  PMID: 39062547 RESULT

• Congdon EE, Ji C, Tetlow AM, Jiang Y, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease: current status and future directions. Nat Rev Neurol. 2023 Dec;19(12):715-736. doi: 10.1038/s41582-023-00883-2. Epub 2023 Oct 24.

  PMID: 37875627 RESULT

• 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.

  PMID: 34998485 RESULT

• Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer's disease. Lancet. 2021 Apr 24;397(10284):1577-1590. doi: 10.1016/S0140-6736(20)32205-4. Epub 2021 Mar 2.

  PMID: 33667416 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 1, 2024
• Study Start: January 7, 2025
• Primary Completion: March 10, 2026
• Study Completion: April 10, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)