Hippocampal Stimulation in Chronic Low Back Pain

Study Overview
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Brief Summary
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In this study the investigators aim to examine the effects of Transcranial Magnetic Stimulation (TMS) on hippocampal network connectivity and pain levels in individuals with chronic low back pain.

Official Title
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Enhancing Cortical-hippocampal Functional Connectivity as a Novel Means for Relieving Chronic Low Back Pain

Conditions
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Back Pain, Chronic Pain, Pain

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation
* Device: Sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 6 months of back pain on a daily basis; male or female with no racial or ethnic restrictions; 18 to 75 years old; average back pain intensity > 4/10 at study entry; must be able to read, understand, and sign consent form; generally healthy. Exclusion Criteria: back pain with fever, chills, rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, history of tumor in the back; back surgery within the past 6 months; Chronic neurologic conditions, e.g., Parkinson's involvement in litigation regarding back pain; other severe medical diseases; pregnancy; positive urinary screen for any recreational drugs, opioids use; use of anticoagulants (low dose ASA allowed); history of gastric ulcer; renal insufficiency or congestive heart failure, contraindication to MRI, contraindication to TMS; including history of seizure/epilepsy* Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk; In the judgment of the investigator, unable or unwilling to follow protocol and instructions; Diagnosis of major depression; Intra-axial implants (e.g. spinal cord stimulators or pumps)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All participants will receive the 2 modalities of stimulation (hippocampal and sham-TMS). Each stimulation round is composed by 5 daily sessions of stimulation, participants will not know which round is active and which is sham. The order of the stimulation modalities will be different across subjects. Subjects will be randomly assigned to one of two possible modality order according to the entrance in the study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hippocampus-stimulation<br>Active high-frequency rTMS (20 Hz pulse trains) | Device: Transcranial Magnetic Stimulation<br>* For the brain stimulation the investigators will use Repetitive Transcranial Magnetic stimulation (rTMS). Different stimulation conditions (hippocampal or sham) will be delivered in each round of stimulation (5 days). Repetitive TMS will be applied at 100% resting motor threshold intensity, 20 Hz pulse trains separated by 28-s inter-train intervals ( 20 minutes for the entire daily stimulation session). Stimulation parameters will be identical in both groups<br>|
| Experimental: Sham-stimulation<br>Sham rTMS | Device: Sham rTMS<br>* Sham rTMS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pain Scales | The endpoint will be the severity of pain measured by changes in the Numeric Rating Scale (NRS) scores before and after each stimulation round. The NRS is a pain screening tool that assesses pain severity during assessment using a 0-10 scale, where zero means no pain and ten means the worst pain imaginable. Higher values indicate a worse outcome. | Pain is assessed at baseline, end of first intervention and end of the second intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hippocampal Connectivity | Changes in hippocampal network connectivity will be evaluated by using resting state functional magnetic resonance (fMRI) before and after hippocampal stimulation. Hippocampal connectivity measurements - regions involved in the network and the parietal target - will be compared before stimulation (baseline) to after stimulation (after active hippocampal stimulation). | approximately 6 weeks - Baseline and after the end of hippocampal stimulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial magnetic stimulation, resting state MRI