Brain Connectomic Mechanisms of Spinal Manipulative Therapy on LDH Analgesia Based on Multimodal MRI

Обзор

Low back and leg pain caused by lumbar disc herniation (LDH) is common. Lever positioning manipulation (LPM) is a spinal manual therapy used to relieve this pain, but how it affects the brain is unclear. This study will compare active LPM with a sham procedure and use multimodal magnetic resonance imaging (MRI) to investigate changes in brain networks associated with pain relief. A total of 84 adults with LDH will be randomly assigned in a 1:1 ratio to active LPM or sham LPM, with three sessions per week for 12 weeks. An additional 42 age- and sex-matched healthy adults will undergo baseline assessments without treatment. Participants with LDH will be assessed before treatment, immediately after the first session, at week 6, and at week 12. Outcomes include pain intensity, lumbar function, disability, adverse events, and MRI measures of functional and structural brain connectivity. The study aims to identify brain connectomic mechanisms associated with LPM-induced analgesia.

Подробное описание

This is a single-center, prospective, randomized, participant- and outcome-assessor-masked, sham-controlled study with a matched healthy control cohort. Eighty-four participants with lumbar disc herniation will be randomly allocated 1:1 to active lever positioning manipulation or sham lever positioning manipulation using a computer-generated block randomization sequence prepared by an independent statistician. Allocation will be concealed in sequentially numbered, opaque, sealed envelopes. Forty-two age- and sex-matched healthy controls will complete baseline clinical and MRI assessments only.

Active and sham treatments will be delivered three times weekly for 12 weeks, with approximately 20 minutes per session. The sham procedure will reproduce the treatment setting, participant position, preparatory procedures, and practitioner contact but will omit the rapid lever-pulling maneuver. Analgesics, neurotrophic drugs, sedatives, spinal manipulation, acupuncture, traction, and other therapies that could affect pain or MRI outcomes will be prohibited during the treatment period.

Participants with LDH will be assessed at baseline before randomization, immediately after the first treatment session, at week 6, and at week 12. The primary outcome is change in pain intensity measured by the Visual Analog Scale from baseline to week 12. Secondary clinical outcomes include lumbar function measured by the Japanese Orthopaedic Association score and disability measured by the Oswestry Disability Index. Multimodal MRI will be used to evaluate longitudinal changes in functional network topology, white-matter structural connectivity, and structure-function coupling. Exploratory analyses will examine gray-matter covariance and associations between clinical improvement and imaging changes. Safety will be assessed through adverse-event monitoring and vital-sign checks at each treatment session.

Вмешательства

• Процедура Active Lever Positioning Manipulation
  Delivered three times weekly for 12 weeks, approximately 20 minutes per session, by an experienced rehabilitation practitioner. With the participant's hips and knees flexed and legs crossed, the practitioner identifies the target lumbar segment, stabilizes it with the elbow, holds the ankles, and lifts and pulls the legs upward and inward to the pre-thrust position. A rapid lever-pulling maneuver is then performed while the participant exhales.
• Процедура Sham Lever Positioning Manipulation
  Delivered three times weekly for 12 weeks, approximately 20 minutes per session, in the same setting and position as the active procedure. Preparatory positioning and practitioner contact are reproduced, but no rapid lever-pulling maneuver is performed. The position is held for 30 seconds with a 15-cm elastic lumbar belt placed around the lower abdomen and pelvis at L4-S1, light hand contact on the ankles, and gradual release.

Первичные конечные точки

• Change in Pain Intensity Measured by the Visual Analog Scale (VAS) [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12; primary endpoint at week 12]

Вторичные конечные точки (5)

• Change in Lumbar Function Measured by the Japanese Orthopaedic Association (JOA) Score [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12]
• Change in Disability Measured by the Oswestry Disability Index (ODI) [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12]
• Change in Resting-State Functional Brain Network Topology [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12]
• Change in White-Matter Structural Connectivity [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12]
• Change in Brain Structure-Function Coupling [Срок оценки: Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12]

Критерии участия

Критерии включения

Patients with lumbar disc herniation (LDH):

• Diagnosis of LDH based on clinical symptoms, physical examination findings, and lumbar imaging consistent with neurological localization; central, paracentral, far-lateral, foraminal, or subarticular lumbar disc protrusion.
• Aged 18-65 years, of either sex, and right-handed.
• In the non-acute phase of LDH, with symptom duration of more than 2 weeks.
• Visual Analog Scale (VAS) score greater than 4 and Japanese Orthopaedic Association (JOA) score less than 15.
• No use of analgesics, neurotrophic drugs, or sedatives within 1 month before enrollment.
• No systematic treatment, spinal manipulation, or other physical therapies within 1 month before enrollment.
• Able to understand the study procedures and complete clinical assessments and MRI scans.
• Provides written informed consent.

Healthy controls:

• Aged 18-65 years, of either sex, and right-handed.
• No history of LDH or chronic low back pain.
• No current pain condition requiring treatment.
• No neurological or psychiatric disorders.
• No known structural brain abnormalities.
• No MRI contraindications.
• Able to complete clinical assessments and MRI scans.
• Provides written informed consent.

Критерии исключения

Patients with LDH:

• Low back pain or sciatica caused by conditions other than LDH.
• Lumbar spondylolisthesis, lumbar tumor, spinal tuberculosis, severe osteoporosis, or localized lumbar skin lesions that may interfere with treatment.
• Severe cardiovascular, cerebrovascular, hepatic, renal, hematopoietic, neurological, or psychiatric disease.
• History of severe head trauma, loss of consciousness, or known structural brain abnormality.
• Impaired consciousness, severe visual or hearing impairment, speech disorder, or inability to complete clinical assessments.
• Non-MRI-compatible metal implants, implanted electronic devices, cardiac pacemakers, severe claustrophobia, or inability to tolerate MRI scanning.
• Asymptomatic LDH.
• Pregnancy, lactation, or planned pregnancy during the study period.
• Participation in another clinical trial within the previous 3 months.
• Any condition judged by the investigators to make the patient unsuitable for participation.

Healthy controls:

• Any condition that may affect eligibility, MRI safety, or data quality.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Third Affiliated Hospital of Zhejiang Chinese Medical University — Ханчжоу

Идентификаторы

NCT: NCT07728149 · ZSLL-KY-20222-049-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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