Brain Connectomic Mechanisms of Spinal Manipulative Therapy on LDH Analgesia Based on Multimodal MRI
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.
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Lijiang Lv
- 電話番号：+86-18958107858
- メール：lvlijiang0288@163.com
研究場所
-
-
Zhejiang
-
Hangzhou、Zhejiang、中国、310053
- The Third Affiliated hospital of Zhejiang Chinese Medical University
-
コンタクト：
- Lijiang Lv
- 電話番号：+86-18958107858
- メール：lvlijiang0288@163.com
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
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.
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Active Lever Positioning Manipulation
Participants with lumbar disc herniation receive active lever positioning manipulation three times per week for 12 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.
|
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.
|
|
偽コンパレータ：Sham Lever Positioning Manipulation
Participants with lumbar disc herniation receive sham lever positioning manipulation three times per week for 12 weeks, approximately 20 minutes per session.
The sham procedure reproduces the treatment setting, position, preparatory procedures, and practitioner contact but omits the rapid lever-pulling maneuver.
|
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.
|
|
介入なし：Matched Healthy Controls
Age- and sex-matched healthy adults undergo baseline clinical assessment and multimodal MRI only.
They receive no study intervention and provide a reference for baseline brain connectivity measures.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Pain Intensity Measured by the Visual Analog Scale (VAS)
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12; primary endpoint at week 12
|
Pain intensity will be assessed using the Visual Analog Scale (VAS).
The prespecified primary endpoint is the between-group difference between active LPM and sham LPM in change from baseline to week 12. VAS will also be collected immediately after the first treatment session and at week 6.
|
Baseline, immediately after the first treatment session, week 6, and week 12; primary endpoint at week 12
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Lumbar Function Measured by the Japanese Orthopaedic Association (JOA) Score
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12
|
Lumbar neurological and functional status will be assessed using the Japanese Orthopaedic Association (JOA) score.
Change from baseline will be compared between the active LPM and sham LPM groups.
|
Baseline, immediately after the first treatment session, week 6, and week 12
|
|
Change in Disability Measured by the Oswestry Disability Index (ODI)
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12
|
Disability related to low back pain will be assessed using the Oswestry Disability Index (ODI), a patient-reported measure of limitations in daily activities.
Change from baseline will be compared between the active LPM and sham LPM groups.
|
Baseline, immediately after the first treatment session, week 6, and week 12
|
|
Change in Resting-State Functional Brain Network Topology
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12
|
Resting-state functional MRI will be parcellated using the 116-region Automated Anatomical Labeling atlas.
Pearson correlation matrices and graph-theoretical metrics reflecting network integration, segregation, and nodal importance will quantify functional topology.
Longitudinal change will be compared between active LPM and sham LPM.
|
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
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12
|
Diffusion tensor imaging will be parcellated with the 116-region Automated Anatomical Labeling atlas.
Whole-brain deterministic streamline tractography will generate structural networks.
Edges will be weighted by mean fractional anisotropy along streamlines connecting region pairs, with absent connections coded as zero.
Longitudinal change will be compared between active LPM and sham LPM.
|
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
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12
|
Functional and white-matter structural connectivity matrices will use the same 116-region Automated Anatomical Labeling parcellation.
For each participant, structure-function coupling will be quantified by the correspondence between functional and structural edge weights across the connectome.
Longitudinal change will be compared between active LPM and sham LPM.
|
Baseline, immediately after the first treatment session, week 6, and week 12; main longitudinal comparison from baseline to week 12
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Group-Level Gray-Matter Structural Covariance Networks
時間枠：Baseline, immediately after the first treatment session, week 6, and week 12; exploratory longitudinal comparison from baseline to week 12
|
High-resolution T1-weighted images will be segmented, and gray-matter volume will be extracted for each Automated Anatomical Labeling region.
Group-level structural covariance networks will be constructed from interregional covariance in gray-matter volume after adjustment for relevant demographic and anatomical covariates.
This exploratory measure will be interpreted at the group level rather than as an individual biomarker.
|
Baseline, immediately after the first treatment session, week 6, and week 12; exploratory longitudinal comparison from baseline to week 12
|
|
Association Between Changes in Connectome Metrics and Clinical Outcomes
時間枠：Baseline through week 12; change scores for the main exploratory association calculated from baseline to week 12
|
Exploratory Spearman rank correlation analyses will assess whether changes in individual-level functional network topology, white-matter structural connectivity, and structure-function coupling are associated with changes in Visual Analog Scale, Japanese Orthopaedic Association, and Oswestry Disability Index scores.
The Benjamini-Hochberg false discovery rate procedure will control for multiple comparisons.
|
Baseline through week 12; change scores for the main exploratory association calculated from baseline to week 12
|
|
Incidence of Adverse Events
時間枠：From the first treatment session through the end of the 12-week intervention
|
The number and proportion of participants experiencing adverse events will be recorded.
Any undesirable medical occurrence will be documented regardless of causal relationship, and severity and relationship to the intervention will be assessed.
Vital signs and treatment-related discomfort or safety concerns will be checked at each treatment session; serious adverse events will be reported according to institutional requirements.
|
From the first treatment session through the end of the 12-week intervention
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- ZSLL-KY-20222-049-02
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。