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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Visual Analogue Scale (VAS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
TI Group
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.
Intervention: Dual-carrier-frequency transcranial alternating current stimulation (Device)
TI-iTBS Group
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.
Intervention: Dual-carrier-frequency transcranial alternating current stimulation (Device)
tES Group
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.
Intervention: Transcranial electrical stimulation (tES) (Device)
Sham group
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.
Intervention: Dual-carrier-frequency transcranial alternating current stimulation (Device)
Outcomes
Primary Outcomes
Visual Analogue Scale (VAS)
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
Secondary Outcomes
- 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),)
- Functional Near-Infrared Spectroscopy (fNIRS)(Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4))
- Surface Electromyography (sEMG)(Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4))
- Hamilton Depression Scale (HAMD)(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))
- Hamilton Anxiety Scale (HAMA)(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))
- McGill Pain Questionnaire (MPQ)(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))
- Oswestry Disability Index (ODI)(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))
- Pittsburgh Sleep Quality Index (PSQI)(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))
- Electroencephalography (EEG)(Pre-enrollment (T0), immediately after the first intervention (T1), end of the 2-week intervention (T3), and 2-week follow-up (T4))