A Study on the Efficacy of Dual-Carrier-Frequency Transcranial Alternating Current Stimulation Modulating the Hippocampus for the Treatment of Chronic Non-Specific Low Back Pain

NCT07832188 | Recruiting

• 1 other identifier: KYLL-2026-06-017-1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Visual Analogue Scale (VAS)

  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

  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)

Secondary Outcomes (13)

• Ultrasound

  Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)

• Motion Sensors

  Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)

• Central Sensitization Inventory (CSI)

  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)

• Magnetoencephalography (MEG)

  Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4)

• Functional Magnetic Resonance Imaging (fMRI)

  Pre-enrollment (T0),end of the 2-week intervention (T3),

Study Arms (4)

TI Group

EXPERIMENTAL

Interference currents of 2 kHz and 2.010 kHz are delivered through scalp electrodes to produce a 10 Hz modulation effect in the right hippocampus. The stimulation current is gradually increased from 0.5 mA to 2 mA, and electrode placement is optimized using a head model. A total of 10 sessions are administered (5 sessions per week for 2 weeks), with routine pain rehabilitation performed immediately after each session.

Device: Dual-carrier-frequency transcranial alternating current stimulation

TI-iTBS Group

ACTIVE COMPARATOR

In addition to the parameters used in the TI group, an intermittent theta-burst stimulation (iTBS) pattern is superimposed. All other parameters, including current intensity, target region, treatment frequency, total course, and subsequent rehabilitation, are identical to those of the TI group.

Device: Dual-carrier-frequency transcranial alternating current stimulation

tES Group

ACTIVE COMPARATOR

Cortical electrical stimulation is applied, with electrodes primarily placed over the primary somatosensory cortex (S1 region) to activate superficial cortical layers and modulate the sensorimotor network. Stimulation intensity is set within the tolerated range. Each session lasts 20 minutes, and the treatment frequency, total course, and subsequent rehabilitation are consistent with those of the previous two groups.

Device: Transcranial electrical stimulation (tES)

Sham group

SHAM COMPARATOR

Electrode placement and the operational procedures are identical to those of the TI group. However, the current output during the treatment is 0 mA, with only the onset and offset sensations of stimulation being simulated, and no effective frequency difference or envelope modulation is generated. The treatment course, frequency, and subsequent rehabilitation are the same as those of the other groups, aiming to maintain blinding without producing any neuromodulatory effects.

Device: Dual-carrier-frequency transcranial alternating current stimulation

Interventions

Dual-carrier-frequency transcranial alternating current stimulation DEVICE

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

Also known as: Temporal interference (TI)

Sham group; TI Group; TI-iTBS Group

Transcranial electrical stimulation (tES) DEVICE

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.

tES Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years;
• Meets the diagnostic criteria for non-specific low back pain as specified in the Chinese Clinical Guidelines for the Diagnosis and Treatment of Non-specific Low Back Pain (2022) ;
• Diagnosed with chronic non-specific low back pain within the past 3 months, or pain located between T12 and the gluteal fold for at least half of the days within the past 6 months;
• VAS score ≥ 3 (Visual Analogue Scale, 0-10);
• Mechanical pain induced by posture, activity, and movement (e.g., flexion and functional movement tasks);
• Voluntarily agrees to participate in this study and has signed the informed consent form.

You may not qualify if:

• Clear etiology of specific low back pain, such as vertebral fracture, severe spinal cord/nerve root compression symptoms (progressive neurological deficit), spinal infection, tumor, ankylosing spondylitis, etc.;
• Prior major lumbar surgery or implants (e.g., internal fixation, spinal cord stimulation devices, etc.), or recent (within 3 months) invasive analgesic treatments such as nerve blocks or radiofrequency ablation;
• Contraindications to MEG or MRI, including the presence of ferromagnetic metal implants in the body (e.g., cardiac pacemakers, hearing aids, carotid artery stents, etc.), claustrophobia that precludes MEG examination, or failed MEG acquisition;
• History of severe cardiovascular disease, epilepsy, or other conditions that contraindicate electrical stimulation;
• Pregnancy or lactation;
• Cognitive impairment, psychiatric disorders, or other conditions that prevent understanding or compliance with the study procedures;
• Rheumatic diseases, connective tissue diseases, or diabetes.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu hospital, Jinan, Shangdong

Jinan, Shandong, 250000, China

RECRUITING

Related Publications (25)

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MeSH Terms

Conditions

Chronic Pain

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Xiaofei Zhang

CONTACT

86-15563139097; xfeizhang2025@163.com

Study Design

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

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: September 21, 2026
• Study Start: July 3, 2026
• Primary Completion (Estimated): September 24, 2029
• Study Completion (Estimated): September 24, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)