Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment (TIS)
A Randomized, Sham-Controlled Trial of Temporal Interference Stimulation Treatment in Patients With Cognitive Impairment
This study aims to evaluate the efficacy and safety of temporal interference stimulation (TIS), a non-invasive neuromodulation technique, in improving cognitive function in patients with cognitive impairment. TIS uses two high-frequency currents applied transcranially, which intersect within the brain to generate a low-frequency modulation field. This technique selectively modulates deep brain regions while minimizing the stimulation of superficial cortical layers.
Participants will undergo individualized MRI-based modeling to determine the optimal electrode placement and stimulation parameters. The intervention consists of 10 stimulation sessions over a period of 14 days, using either active TIS or sham stimulation. Cognitive assessments, EEG recordings, and functional MRI scans will be conducted at baseline; 5 days after intervention initiation; at the end of the 10-day intervention; and during follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention to evaluate both immediate and long-term effects on cognitive performance and neural activity.
The study aims to determine whether TIS can serve as a feasible and effective neuromodulation strategy for individuals with cognitive impairment.
調査の概要
状態
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Mou Zhehui
- 電話番号：+86 18959257015
- メール：muzhehui@gmail.com
研究場所
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Tianjin Municipality
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Tianjin、Tianjin Municipality、中国
- 募集
- Tianjin Huanhu Hospital
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コンタクト：
- Li Pan, Director
- 電話番号：+86 13114881943
- メール：doc_panpan@163.com
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- meets the criteria for probable AD and MCI due to AD as defined by the 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines;
- Positive amyloid biomarker (amyloid PET or CSF tTau/Aβ 42);
- Positive tau biomarker (tau-PET or CSF pTau181);
- AD-related standard treatments (acetyl cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists) taken at a stable dose for at least 12 weeks prior to baseline.
- meets the criteria for probable bvFTD as defined by the revised diagnostic criteria for the behavioural variant of frontotemporal dementia (2011), or PPA as defined by the Classification of primary progressive aphasia and its variants (2011);
- Optional genetic confirmation of FTD-related pathogenic mutations (if available).
- Aged between 45 and 85 years, inclusive; no gender limitation.
- Right-handed.
- Education level ≥ 3 years.
- Mini-Mental State Examination (MMSE) score ≥ 11.
- Clinical Dementia Rating (CDR) score of 1 or 2.
- with a reliable caregiver
- Able to cooperate with cognitive assessments and cognitive training procedures.
- Full understanding of the study, voluntary participation, and provision of written informed consent approved by the Ethics Committee.
Exclusion Criteria:
- Diagnosis of other types of dementia or major neurological disorders (e.g., stroke, epilepsy, Lewy body dementia, vascular dementia, Parkinson's disease dementia, Huntington's disease).
- Major psychiatric disorders such as severe depression or anxiety.
- Severe systemic or organ dysfunction (e.g., heart failure III-IV, liver cirrhosis, renal failure).
- Use of medications that significantly affect cognition (e.g., anticholinergics, sedatives), unless approved by the physician.
- Presence of metal implants incompatible with MRI or TIS (e.g., pacemakers, deep brain stimulators).
- Skull defects or cranial abnormalities.
- Inability to tolerate EEG or head stabilization.
- Severe visual or hearing impairment preventing task performance.
- History of alcohol or drug abuse.
- Participation in another clinical trial within the past 3 months.
- Current or recent treatment with anti-amyloid monoclonal antibodies (e.g., lecanemab, donanemab).
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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偽コンパレータ：Sham TIS + Active TIS + Targeted Cognitive Training
Participants will receive sham temporal interference stimulation during the first 5 days, followed by active temporal interference stimulation during the next 5 days.
Targeted cognitive training will be administered during the intervention period.
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Temporal interference stimulation will be delivered using two high-frequency alternating currents at 2000 Hz and 2100 Hz, generating a low-frequency envelope. Stimulation will be delivered in a theta-burst-like pattern with 2 seconds on and 8 seconds off. Frontal and temporal targets will be stimulated sequentially. In the sham-controlled group, participants will receive active stimulation during Days 6-10 following 5 days of sham stimulation. In the active stimulation groups, participants will receive active stimulation throughout the entire 10-day intervention period. Two sessions will be administered per day, with each session lasting 40 minutes.
Sham stimulation will use two identical high-frequency currents of 2000 Hz and 2000 Hz, producing no frequency difference and no modulation envelope.
The stimulation timing, electrode placement, and procedures will be consistent with active stimulation to maintain blinding.
In the sham-controlled group, sham stimulation will be administered during Days 1-5 before switching to active stimulation.
Participants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives.
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実験的：Active TIS + Active TIS + Targeted Cognitive Training
Participants will receive active temporal interference stimulation during the first 5 days and the next 5 days.
Targeted cognitive training will be administered during the intervention period.
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Temporal interference stimulation will be delivered using two high-frequency alternating currents at 2000 Hz and 2100 Hz, generating a low-frequency envelope. Stimulation will be delivered in a theta-burst-like pattern with 2 seconds on and 8 seconds off. Frontal and temporal targets will be stimulated sequentially. In the sham-controlled group, participants will receive active stimulation during Days 6-10 following 5 days of sham stimulation. In the active stimulation groups, participants will receive active stimulation throughout the entire 10-day intervention period. Two sessions will be administered per day, with each session lasting 40 minutes.
Participants will complete structured cognitive training tasks designed to engage specific cognitive processes associated with the study objectives.
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アクティブコンパレータ：Active TIS + Active TIS + General Cognitive Training
Participants will receive active temporal interference stimulation during the first 5 days and the next 5 days.
General cognitive training will be administered during the intervention period.
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Temporal interference stimulation will be delivered using two high-frequency alternating currents at 2000 Hz and 2100 Hz, generating a low-frequency envelope. Stimulation will be delivered in a theta-burst-like pattern with 2 seconds on and 8 seconds off. Frontal and temporal targets will be stimulated sequentially. In the sham-controlled group, participants will receive active stimulation during Days 6-10 following 5 days of sham stimulation. In the active stimulation groups, participants will receive active stimulation throughout the entire 10-day intervention period. Two sessions will be administered per day, with each session lasting 40 minutes.
Participants will complete general cognitive training tasks involving multiple cognitive domains without specifically emphasizing the primary targeted cognitive process.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Changes from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Measures global cognitive function. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a clinician-administered scale commonly used to assess cognitive performance in individuals with cognitive impairment and dementia. Full Scale Name: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Typical Total Score Range: 0 to 70. Higher Scores Mean: Greater cognitive impairment (worse cognitive performance). |
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Cross-frequency Neural Oscillations
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Electrophysiological indices of cross-frequency neural interactions will be quantified using electroencephalography (EEG).
Measures will include phase-amplitude coupling (PAC) between low-frequency and high-frequency bands (e.g., theta-gamma and alpha-gamma coupling), cross-frequency coherence, and power modulation across frequency bands.
These metrics reflect the integrity of neural communication and network coordination within cognition-related brain systems.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Change from baseline in resting-state frontal-temporal EEG functional connectivity strength
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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After EEG preprocessing, frequency-band decomposition, and functional connectivity analysis, functional connectivity strength within frontal regions, within temporal regions, and between frontal and temporal regions will be calculated.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Frontal and Temporal Gray Matter Density (sMRI)
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in gray matter density or volume within frontal and temporal brain regions, quantified using structural Magnetic Resonance Imaging (sMRI).
This measure assesses the structural integrity and potential neuroplastic changes, including cortical thinning or gray matter increase, in brain regions critically involved in executive function, language processing, and memory-related cognitive processes.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Cortical Thickness (sMRI)
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in cortical thickness across various brain regions, quantified using structural Magnetic Resonance Imaging (sMRI).
This measure assesses the integrity and potential thinning or thickening of the cerebral cortex.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in ALFF
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Resting-state fMRI will be used to quantify changes in the amplitude of low-frequency fluctuations (ALFF) within frontal and temporal brain regions following intervention.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in ReHo
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Resting-state fMRI data will be analyzed to evaluate changes in regional homogeneity (ReHo), reflecting local synchronization of spontaneous neural activity within frontal and temporal regions.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in resting-state functional connectivity
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in resting-state functional connectivity between frontal and temporal brain regions using fMRI, reflecting synchronized neural activity within memory and attention-related networks.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in FA
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in fractional anisotropy (FA) in white matter tracts using diffusion tensor imaging (DTI), reflecting directional water diffusion and white matter integrity.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in MD
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in mean diffusivity (MD) in white matter tracts using DTI, reflecting overall magnitude of water diffusion.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in AD
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in axial diffusivity (AD) in white matter tracts using DTI, reflecting diffusion along the principal axis of fibers.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from baseline in RD
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Evaluation of changes in radial diffusivity (RD) in white matter tracts using DTI, reflecting diffusion perpendicular to fiber orientation and potential demyelination.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Mini-Mental State Examination (MMSE) Score
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Measures global cognitive function.
Full Scale Name: Mini-Mental State Examination (MMSE) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Montreal Cognitive Assessment - Basic (MoCA-B) Score
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Measures global cognitive function.
Full Scale Name: Montreal Cognitive Assessment - Basic (MoCA-B) Minimum Value: 0 Maximum Value: 30 Higher Scores Mean: A better global cognitive function.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Clinical Dementia Rating (CDR) Score
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Measures global cognitive and functional status using the Clinical Dementia Rating (CDR) scale, which assesses cognitive performance and daily functioning across multiple domains, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR provides a global rating of dementia severity based on structured interviews with the participant and an informant, reflecting overall cognitive impairment and functional impact. |
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in Zarit Caregiver Burden Interview (ZBI) Score
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Assesses perceived caregiver burden. The Zarit Caregiver Burden Interview (ZBI) is a widely used, caregiver-reported questionnaire designed to evaluate the level of burden experienced by individuals providing care to persons with cognitive impairment or other chronic conditions. The scale assesses emotional, physical, social, and financial aspects of caregiver strain. Total Score Range: 0 to 88. Higher Scores Mean: Greater caregiver burden. Change in ZBI score from baseline to each assessment time point will be analyzed. |
Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Changes from Baseline in AD Molecular Pathologies and Blood Biomarkers
時間枠：Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Plasma concentrations of Alzheimer's disease-related biomarkers-including the Aβ42/40 ratio, phosphorylated tau-217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-will be quantified using validated immunoassay platforms.
These biomarkers reflect amyloid pathology, tau phosphorylation, axonal injury, and astroglial activation, respectively.
Changes from baseline will be assessed to evaluate peripheral biochemical responses to the intervention.
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Baseline; 5 days after intervention initiation; end of the 10-day intervention; and follow-up assessments at 4 weeks, 8 weeks, and 12 weeks post-intervention.
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Incidence and Severity of Adverse Events (AEs)
時間枠：Through study completion, an average of 14 weeks
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Monitoring and reporting of all adverse events and serious adverse events related to the intervention, including their frequency, severity, and relationship to the study intervention
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Through study completion, an average of 14 weeks
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協力者と研究者
スポンサー
出版物と役立つリンク
一般刊行物
- Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
- Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.
- Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
- Beanato E, Moon HJ, Windel F, Vassiliadis P, Wessel MJ, Popa T, Pauline M, Neufeld E, De Falco E, Gauthier B, Steiner M, Blanke O, Hummel FC. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci Adv. 2024 Nov;10(44):eado4103. doi: 10.1126/sciadv.ado4103. Epub 2024 Oct 30.
- Li LM, Violante IR, Leech R, Ross E, Hampshire A, Opitz A, Rothwell JC, Carmichael DW, Sharp DJ. Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation. Hum Brain Mapp. 2019 Feb 15;40(3):904-915. doi: 10.1002/hbm.24420. Epub 2018 Oct 30.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TJHH-CI-TIS-2025-12
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
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この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
FTDの臨床試験
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Azienda Ospedaliero-Universitaria di ModenaAzienda Ospedaliero-Universitaria Careggi; University of Modena and Reggio Emilia; A.O.U. Città... と他の協力者募集
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The Bluefield Project to Cure Frontotemporal DementiaMayo Clinic; University of California, San Francisco積極的、募集していない
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Passage Bio, Inc.積極的、募集していない前頭側頭型認知症 | FTD | C9orf72 | 認知症前頭側頭 | FTD-GRNアメリカ, ポルトガル, カナダ, オーストラリア, ブラジル
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AviadoBio Ltd募集前頭側頭型認知症 | FTD | FTD-GRN | 認知症、前頭側頭オランダ, アメリカ, イギリス, スペイン, ベルギー, スウェーデン, カナダ, ポーランド, イタリア
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Faculty Hospital Kralovske Vinohrady招待による登録認知症 | 軽度認知障害 (MCI) | 前頭側頭変性症（FTD） | アルツハイマー病 (AD) | 軽度認知障害（MCI）amnestチェコ
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Università degli Studi di Brescia募集FTD | FTLD | PPA | rTMS | PSP | 皮質基底症候群（CBS） | bvFTD | シータバースト刺激イタリア
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Fondazione I.R.C.C.S. Istituto Neurologico Carlo...募集ALS（筋萎縮性側索硬化症） | 特発性頭蓋内圧亢進症 | 神経障害 | 精神障害 | FTD | 前頭側頭型認知症（FTD）イタリア
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IRCCS Centro San Giovanni di Dio Fatebenefratelli募集
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University of California, San FranciscoNational Institute of Neurological Disorders and Stroke (NINDS); National Center for Advancing... と他の協力者完了筋萎縮性側索硬化症（ALS） | 進行性核上性麻痺（PSP） | 皮質基底核変性症 (CBD) | FTLD | 前頭側頭型認知症（FTD） | PPA症候群 | 行動バリアント前頭側頭型認知症 (bvFTD) | セマンティックバリアント原発性進行性失語症 (svPPA) | 非流暢性バリアント原発性進行性失語症 (nfvPPA) | 筋萎縮性側索硬化症を伴う FTD (FTD/ALS) | オリゴ症候性 PSP (oPSP) | 皮質基底核症候群 (CBS)アメリカ, カナダ
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University of Campania Luigi Vanvitelli募集認知症 | 軽度認知障害 (MCI) | アルツハイマー病 | アルツハイマー病、早期発症 | 前頭側頭変性症（FTD） | 神経認知機能の低下イタリア
Temporal Interference Stimulationの臨床試験
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Biotronik SE & Co. KG完了
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University Hospital, Strasbourg, France完了
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Biotronik SE & Co. KG完了心臓ペーシング、人工ドイツ, イスラエル, 香港, オーストリア, チェコ共和国, オーストラリア, ブラジル, カナダ, スロバキア, スペイン