Clinical Study on the Safety and Efficacy of Temporal Interference Stimulation in the Treatment of Post-Stroke Aphasia

Overview

Neurological disorders encompass a wide variety of diseases, including congenital and neurodevelopmental disorders, cerebrovascular and neurodegenerative diseases, nervous system infections, neuroimmune diseases, neuromuscular or peripheral nervous system disorders, traumatic injuries, and tumor-related neurological conditions, with diverse symptomatic manifestations. The etiology, symptoms, and disease courses of these disorders vary significantly, severely impacting human health and social development, and have become a critical global public health issue. Some neurological disorders can lead to lifelong disability or high mortality rates, while others remain poorly understood, lacking effective treatments or cures. Post-stroke aphasia (PSA) is an acquired language impairment caused by ischemic or hemorrhagic injuries to the central nervous system. Its clinical manifestations are diverse, potentially affecting spontaneous speech, auditory comprehension, repetition, naming, reading, and writing abilities, among other aspects. Statistics indicate that over 16 million people worldwide suffer from stroke each year, with approximately 38% of survivors experiencing aphasia. The prognosis for this condition is concerning, as more than 40% of patients still exhibit significant language impairments one year after the stroke, with some even facing lifelong effects. The large patient population, significant communication barriers, and poor prognosis severely diminish patients' quality of life, significantly increasing their risk of emotional disorders such as depression and social isolation. This poses a substantial challenge to family caregiving and public health systems. Therefore, the development of non-invasive and effective novel therapeutic approaches holds substantial scientific and societal importance. Temporal interference stimulation (TI) technology represents a breakthrough in achieving non-invasive deep brain stimulation. This technology is based on the interference phenomenon, utilizing two pairs of surface electrodes to simultaneously apply sinusoidal wave stimuli at 2 kHz and 2.01 kHz. Two cortical regions are exposed to electric fields of 2 kHz or 2.01 kHz, and an interference electric field is generated in the brain region where these two fields overlap, with its envelope oscillating at 10 Hz. This technology has already been applied in the treatment of conditions such as depression, Parkinson's disease, and disorders of consciousness. The primary objective of this study is to explore the effects of TI intervention on deep brain regions, particularly on motor and non-motor related brain networks and functions in patients with neurological disorders, especially post-stroke aphasia. This research aims to provide a potential new approach for improving the clinical symptoms of these patients.

Detailed description

This study plans to recruit 40 patients with neurological disorders and randomly assign them to either a real stimulation treatment group or a sham stimulation treatment group (20 patients per group). The real stimulation treatment group will receive treatment using Temporal Interference Stimulation (TIS) technology. The current frequencies are intended to be 1400 Hz and 1430 Hz. The stimulation duration is 30 minutes; administered once daily for 10 consecutive days. The control group will receive sham stimulation. The sham stimulation group will have the same electrode placement, current intensity, and frequency settings as the TIS group, but without eliciting physiological effects. Randomization will be performed to blind both the patients and the assessors. The order of stimulation targets will be randomized between subjects, while the order of stimulation targets for the same subject will remain consistent throughout the treatment course. Treatment will be administered for 10 consecutive days. Both groups will receive either real or sham stimulation paired simultaneously with standard Speech and Language Therapy (SLT).The observation indicators will be the changes in scores from baseline to post-treatment and follow-up on the following assessments: Western Aphasia Battery (WAB, including fluency and information content), Aphasia Battery of Chinese (ABC,comprising spontaneous speech, auditory comprehension, repetition, naming, reading, writing, structural and spatial functions, application and calculation), Verbal Fluency Test (VFT), Language Assessment Manual (Including True Word Auditory Repetition, Picture Naming, Non-Word Auditory Repetition, Word Reading, Verb-Noun-Picture Matching, Writing), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Brunnstrom stages of stroke recovery, and simplified Fugl-Meyer Assessment of motor function (FMA).

Interventions

• Other temporal interference stimulation
  The envelope frequency of the TIS employed is set at 30 Hz, while the current frequencies are planned to be 1400 Hz and 1430 Hz. Due to individual variability in sensitivity to TIS, we intend to make necessary adjustments to the stimulation frequency or duration during the treatment process. For the continuous stimulation mode of TIS, the protocol follows the post-operative control consensus from Chinese experts in deep brain stimulation for neurological disorders. Electrode placement adheres to
• Behavioral speech and language therapy
  Speech and Language Therapy (SLT) was conducted by a certified Speech-Language Pathologist (SLP), providing standardized language rehabilitation for 40 minutes daily, which included 30 minutes of SLT synchronized with TI. Based on the results of the patients' language assessments, the SLP developed and implemented an individualized rehabilitation treatment plan. The primary rehabilitation methodologies included articulation exercises, phoneme stimulation, Schuell stimulation therapy, melodic int

Primary outcome measures

• Aphasia Battery of Chinese (ABC,comprising spontaneous speech, auditory comprehension, repetition, naming, reading, writing, structural and spatial functions, application and calculation) [Time frame: Baseline;10 days; one-month follow-up]
• Verbal fluency test (VFT) [Time frame: Baseline;10 days; one-month follow-up]
• Western Aphasia Battery (WAB, including fluency and information content) [Time frame: Baseline;10 days; one-month follow-up]

Secondary outcome measures (8)

• Language Assessment Manual (Including True Word Auditory Repetition, Picture Naming, Non-Word Auditory Repetition, Word Reading, Verb-Noun-Picture Matching, and Writing) [Time frame: Baseline;10 days; one-month follow-up]
• Mini Mental State Examination (MMSE) [Time frame: Baseline;10 days;one-month follow-up]
• Montreal Cognitive Assessment (MoCA) [Time frame: Baseline;10 days; one-month follow-up]
• Brunnsrom stages of motor recovery [Time frame: Baseline;10 days; one-month follow-up]
• Fugl-Meyer Assessment Scale (FMA) [Time frame: Baseline;10 days; one-month follow-up]
• Hamilton Anxiety Rating Scale (HAMA) [Time frame: Baseline;10 days; one-month follow-up]
• Hamilton Depression Rating Scale (HAMD) [Time frame: Baseline;10 days; one-month follow-up]
• MRI measures [Time frame: Baseline;10 days; one-month follow-up]

Eligibility criteria

Inclusion criteria

• Diagnosed with post-stroke aphasia;
• Right-handed;
• Native Chinese speaker with comprehension of Mandarin;
• Aged 18-80 years;
• Complete relevant assessment and imaging data;
• Informed consent obtained from the patient and their family.

Exclusion criteria

• Cerebellar involvement in the stroke lesion, and incomplete scanning of cerebellar structures;
• Severe dysarthria;
• Concurrent epilepsy with occasional seizures;
• Implanted pacemaker or deep brain stimulator;
• History of brain tissue resection for prior lesions such as brain tumours or brain abscesses;
• Other severe psychiatric disorders.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT07346378 · AHMU-TI-PSA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗