Qilu hospital, Jinan, Shangdong
Jinan, Shandong, 250000, China
Location status: Recruiting
NCT Number: NCT07832188
This is a single-center, randomized, double-blind, sham-controlled trial evaluating dual-carrier-frequency transcranial alternating current stimulation targeting the hippocampus in 60 patients with chronic non-specific low back pain. Participants will be randomized into four groups: active stimulation, active stimulation with iTBS, superficial stimulation control, and sham control. All groups will receive standard rehabilitation. The intervention is 20 minutes per session, 5 sessions weekly for 2 weeks (10 sessions total).
The primary objective is to assess improvements in pain intensity (VAS) and emotional symptoms (anxiety, depression) at week 2. Exploratory objectives include examining functional connectivity changes between the hippocampus and prefrontal/sensory cortices using fMRI, MEG, and fNIRS, and correlating these with clinical improvements.
Outcomes include VAS (primary), McGill Pain Questionnaire, HAMA, HAMD, ODI, CSI, PSQI, and objective measures (brain imaging, EEG, EMG). Assessments occur at baseline (T0), post-first stimulation (T1), mid-treatment (T2), treatment end (T3), and 2-week follow-up (T4).
Linear mixed-effects models will be used for analysis with multiple comparison correction. This study aims to provide evidence for hippocampal-targeted neuromodulation in chronic non-specific low back pain.
Interested in participating?
Request Info18 year–80 year
All sexes
Interventional
Not applicable
Jinan, Shandong, 250000, China
Location status: Recruiting
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Dual-carrier-frequency transcranial alternating current stimulation is based on the interference principle. Two pairs of carrier-frequency alternating currents with slightly different frequencies are applied to the scalp. After intracranial superposition, the nonlinear response of biological tissues generates a low-frequency envelope-modulated electric field in deep brain regions. This interference electric field oscillates periodically at the difference between the two carrier frequencies, enabling entrainment and modulation of neuronal rhythms in deep structures. This distinguishes it from conventional transcranial electrical stimulation, in which electric field intensity decays exponentially with depth, predominantly affecting superficial cortical layers and having limited efficacy in modulating deep nuclei.
In terms of safety, this technique is a non-invasive stimulation method. Adverse effects are limited to mild tingling or itching at the electrode contact sites, indicating favo
Other names: Temporal interference (TI)
Cortical electrical stimulation is a neuromodulation technique in which electrodes are placed on the surface of the cerebral cortex or over the dura mater to deliver weak electrical currents for direct modulation of local neuronal electrical activity. By either exciting or inhibiting neuronal firing in specific cortical regions, it can regulate functional brain networks and is commonly used in studies on brain function mapping, neurorehabilitation, and pain modulation.
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A 100-mm visual analogue scale is used, with "0" indicating no pain and "10" indicating the worst possible pain; the subject marks the current pain level on the scale, and the distance (mm) from the left end is measured as the VAS score
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A high-frequency linear array ultrasound probe (≥10 MHz) is placed over the erector spinae and multifidus muscles; cross-sectional and longitudinal gray-scale images are acquired in standardized positions, and muscle thickness, cross-sectional area, and echo intensity are measured using image analysis software to assess morphological and structural changes
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
Inertial measurement unit (IMU) sensors integrating tri-axial accelerometers, gyroscopes, and magnetometers are attached to the subject's lumbar region and bilateral lower limbs; continuous data on acceleration, angular velocity, and orientation are collected during standardized walking and trunk movement tasks, and gait parameters, trunk range of motion, and symmetry indices are calculated using dedicated algorithms
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A 25-item self-administered questionnaire is used, with each item scored from 0 to 4 (never to always); the total score ranges from 0 to 100, with higher scores indicating a higher degree of central sensitization
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A whole-head magnetoencephalography system is used to record spontaneous brain magnetic signals in a shielded room during the resting state; source localization algorithms are applied to reconstruct the magnetic signals from the scalp to the intracerebral source space, and spectral power and functional connectivity of the hippocampus and pain-related brain regions are assessed
Time frame: Pre-enrollment (T0),end of the 2-week intervention (T3),
Blood oxygen level-dependent (BOLD) functional imaging is performed using a 3.0T or higher MRI scanner; the subject remains in a resting state during scanning, and functional connectivity is assessed by measuring the temporal synchronization of low-frequency BOLD signal oscillations between brain regions, with a focus on connectivity changes between the hippocampus, prefrontal cortex, and somatosensory cortex
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A multi-channel functional near-infrared spectroscopy system is used, with optodes placed over the scalp regions corresponding to the prefrontal cortex and sensorimotor cortex; changes in oxygenated and deoxygenated hemoglobin concentrations are monitored in real time by measuring near-infrared light attenuation, reflecting regional cerebral functional activity.
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
Surface electrodes are placed symmetrically over the bilateral erector spinae and multifidus muscle bellies; sEMG signals are recorded during standardized functional movements (e.g., trunk flexion and extension), and after amplification, filtering and root mean square (RMS) processing, time-domain and frequency-domain parameters are extracted to assess muscle activation patterns and fatigue
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
The 17-item version of the Hamilton Depression Scale is administered by a trained evaluator through a structured interview; the total score ranges from 0 to 52, with higher scores indicating more severe depressive symptoms.
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
The 14-item version of the Hamilton Anxiety Scale is administered by a trained evaluator through a structured interview; the total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms.
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A standardized self-administered questionnaire comprising sensory, affective, and evaluative dimensions is used; the subject selects the most appropriate pain descriptors based on personal pain experience, and the Pain Rating Index (PRI) and Present Pain Intensity (PPI) scores are calculated
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A 10-item self-administered questionnaire (covering pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling) is used; each item is scored 0-5, and the sum is expressed as a percentage of the maximum possible score (0-100%), with higher percentages indicating more severe disability
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), mid-intervention (T2), end of the 2-week intervention (T3), and 2-week follow-up (T4)
A 19-item self-administered questionnaire comprising 7 component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction) is used; each component is scored 0-3, and the sum yields a global PSQI score (0-21), with a score >5 indicating poor sleep quality
Time frame: Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)
Scalp electroencephalography is recorded using the international 10-20 electrode placement system during both resting and task states; signals are amplified, filtered, and digitized, and power spectral density across frequency bands (δ, θ, α, β, γ) and EEG microstate features are extracted to assess changes in spontaneous neural electrical activity
Contact information is provided by the study sponsor or research team.
Qilu Hospital of Shandong University
Other
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