Cortical Surface Functional Changes After Lever Positioning Manipulation for Lumbar Disc Herniation
Brain Connectomic Mechanisms of Spinal Manipulative Therapy on LDH Analgesia Based on Multimodal MRI
Lever positioning manipulation (LPM) is used to treat pain associated with lumbar disc herniation (LDH), but treatment-associated changes in cortical functional organization remain unclear. This prospective nonrandomized study will examine cortical surface-based resting-state functional magnetic resonance imaging (MRI) measures before and after a 4-week course of LPM.
The target is 30 participants with LDH completing treatment-period assessments and 30 age- and sex-matched healthy controls completing baseline assessment. Participants who withdraw will be replaced as needed, and all enrolled and replacement participants will be counted. Participants with LDH will receive LPM three times weekly for 4 weeks, approximately 20 minutes per session. MRI and clinical scales will be collected before treatment and at week 4 after the first session. Healthy controls will undergo baseline MRI only and receive no intervention. The eight primary imaging outcome groups cover amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), global functional connectivity density, seed-to-vertex connectivity, region-to-region connectivity, within- and between-network connectivity, functional connectivity gradients, and gradient eccentricity. Clinical outcomes include VAS, JOA, ODI, SAS and SDS scores. Adverse events will be monitored throughout treatment.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
This is a prospective, nonrandomized, outcome-assessor-masked interventional study with an LDH group receiving lever positioning manipulation and a healthy control group receiving no intervention. Clinical recruitment and treatment will be conducted at the Third Affiliated Hospital of Zhejiang Chinese Medical University. MRI will be acquired at Zhejiang Hospital in Hangzhou. Group membership is based on disease status. The target is 30 participants completing the required assessments in each group. Participants who withdraw will be replaced as needed; all enrolled participants, withdrawals and replacements will be accounted for in cumulative enrollment and participant flow. The anticipated enrollment estimate will be updated as replacement recruitment requires.
Participants with LDH will receive lever positioning manipulation three times weekly for 4 weeks, approximately 20 minutes per session. The procedure includes segment localization, stabilization, positioning to the pre-thrust point, and a rapid lever-pulling maneuver during exhalation. Outcome assessors will be masked to group assignment; participants and treating practitioners will not be masked. Concomitant medications and therapies will be managed according to the approved protocol.
Participants with LDH will undergo MRI and clinical assessments at baseline before treatment and at week 4 after the first treatment session. Healthy controls will undergo baseline MRI and general eligibility assessments only; they will not receive treatment or complete the patient clinical outcome scales. No additional routine follow-up is planned after the week-4 assessment.
Cortical surface-based resting-state MRI analyses will evaluate eight primary outcome groups: amplitude of low-frequency fluctuations, regional homogeneity, global functional connectivity density, seed-to-vertex functional connectivity, region-to-region functional connectivity, within-network and between-network connectivity, functional connectivity gradient scores, and functional gradient eccentricity. The primary imaging comparison is within-participant change from baseline to week 4 in the LDH group. Healthy controls provide a baseline reference only.
Clinical outcomes will assess pain with the Visual Analog Scale, neurological and functional status with the Japanese Orthopaedic Association score, disability with the Oswestry Disability Index, anxiety symptoms with the Chinese-language Zung Self-Rating Anxiety Scale, and depressive symptoms with the Chinese-language Zung Self-Rating Depression Scale.
Adverse events and vital signs will be assessed at each treatment session throughout the 4-week treatment period. Adverse events will be recorded regardless of causal relationship, and severity and relationship to the intervention will be assessed. Serious adverse events will be reported according to institutional requirements. Prespecified quality-control and statistical procedures will account for the multiple imaging outcome families and missing observations.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Lijiang Lv
- Número de teléfono: +86-18958107858
- Correo electrónico: lvlijiang0288@163.com
Ubicaciones de estudio
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Zhejiang
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Hangzhou, Zhejiang, Porcelana
- Zhejiang Hospital
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Hangzhou, Zhejiang, Porcelana, 310053
- The Third Affiliated Hospital of Zhejiang Chinese Medical University
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Contacto:
- Lijiang Lv
- Número de teléfono: +86-18958107858
- Correo electrónico: lvlijiang0288@163.com
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Patients with lumbar disc herniation:
- 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 score greater than 4 and Japanese Orthopaedic Association 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.
Exclusion Criteria:
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: Lumbar Disc Herniation (LDH)
Participants with lumbar disc herniation receive lever positioning manipulation three times weekly for 4 weeks, approximately 20 minutes per session. Clinical outcome scales and MRI are obtained before treatment and at week 4 after the first session. The target is 30 participants completing the required assessments; withdrawals will be replaced as needed and included in cumulative enrollment. |
Delivered to participants with LDH by an experienced rehabilitation practitioner three times weekly for 4 weeks, approximately 20 minutes per session. 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. |
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Sin intervención: Healthy Controls (HC)
Age- and sex-matched healthy controls undergo baseline eligibility assessment and MRI only, without study intervention or patient clinical outcome scales. The target is 30 participants completing the baseline assessment. Withdrawals before completion will be replaced as needed and included in cumulative enrollment. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Cortical Surface-Based Mean-Normalized Amplitude of Low-Frequency Fluctuations
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Resting-state functional MRI will assess the amplitude of low-frequency blood oxygen level-dependent (BOLD) fluctuations on the cortical surface. Mean-normalized ALFF in the 0.01-0.08 Hz band will be calculated relative to the mean cortical ALFF. Within-participant change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Surface-Based Regional Homogeneity
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Regional homogeneity will be calculated as Kendall's coefficient of concordance between the BOLD time series at each cortical vertex and its one-ring surface neighbors. Scores range from 0 to 1, with higher values indicating greater local temporal concordance. Within-participant change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Surface-Based Global Functional Connectivity Density
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Global functional connectivity density will be quantified as the proportion of other cortical vertices whose BOLD time series have a Pearson correlation greater than 0.6 with each vertex. Self-connections will be excluded. Within-participant change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Surface-Based Seed-to-Vertex Functional Connectivity
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Left and right insular cortex seeds will be defined using independent anatomical labels. Seed-to-vertex functional connectivity will be calculated using Pearson correlation followed by Fisher z transformation. Within-participant change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Region-to-Region Functional Connectivity
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Cortical regions will be defined using the Schaefer 400-region parcellation. Region-to-region functional connectivity will be calculated using Pearson correlation between regional BOLD time series followed by Fisher z transformation. Changes in unique region-pair connectivity values from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Within-Network and Between-Network Cortical Functional Connectivity
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Using the seven Yeo networks, within-network and between-network connectivity will be quantified as mean Fisher-z-transformed region-to-region connectivity. The measures include seven within-network and 21 between-network values. Within-participant changes from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Functional Connectivity Gradient Scores
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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The first three cortical functional connectivity gradients will be estimated from regional connectivity profiles using diffusion-map embedding and aligned to a fixed independent reference. Regional gradient coordinates will be reported in arbitrary units. Within-participant changes from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Cortical Functional Gradient Eccentricity
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Functional gradient eccentricity will be calculated as each cortical region's Euclidean distance from the centroid of all regions in the space of the first three aligned functional gradients. Values will be reported in arbitrary units. Within-participant change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Pain Intensity Measured by the Visual Analog Scale (VAS)
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Pain intensity will be assessed using a 10-cm horizontal Visual Analog Scale, recorded on a 0-10 scale, where 0 indicates no pain and 10 indicates the worst imaginable pain. Change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Lumbar Function Measured by the Japanese Orthopaedic Association (JOA) Score
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Lumbar neurological and functional status will be assessed using the Japanese Orthopaedic Association score, reported on a 0-29 scale. Higher scores indicate better status. Change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Disability Measured by the Oswestry Disability Index (ODI)
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Low-back-pain-related disability will be assessed using the Oswestry Disability Index, reported on a 0-100% scale. Higher scores indicate greater disability. Change from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Anxiety Symptoms Measured by the Zung Self-Rating Anxiety Scale (SAS)
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Anxiety symptoms will be assessed using a Chinese-language version of the 20-item Zung Self-Rating Anxiety Scale. The total raw score ranges from 20 to 80 and is converted to a standard/index score ranging from 25 to 100 by multiplying by 1.25. Higher standard scores indicate more severe anxiety symptoms. Change in standard score from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Change in Depressive Symptoms Measured by the Zung Self-Rating Depression Scale (SDS)
Periodo de tiempo: Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Depressive symptoms will be assessed using a Chinese-language version of the 20-item Zung Self-Rating Depression Scale. The total raw score ranges from 20 to 80 and is converted to a standard/index score ranging from 25 to 100 by multiplying by 1.25. Higher standard scores indicate more severe depressive symptoms. Change in standard score from baseline to week 4 will be assessed in participants with LDH. |
Baseline before treatment and week 4 after the first treatment session in participants with LDH.
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Otras medidas de resultado
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of Adverse Events
Periodo de tiempo: From the first treatment session through the end of the 4-week intervention.
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The number and proportion of participants experiencing adverse events will be recorded throughout the 4-week treatment course. Severity and relationship to intervention will be assessed. Vital signs and treatment-related discomfort will be checked at each treatment session. |
From the first treatment session through the end of the 4-week intervention.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Lijiang Lv, The Third Affiliated hospital of Zhejiang Chinese Medical University
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- LPM-SURFACE-2026-01
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
A decision regarding the sharing of de-identified individual participant data has not yet been made.
Información sobre medicamentos y dispositivos, documentos del estudio
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