Clinical trial NCT06027190: Randomized Controlled Study of Optical 3D Navigated Repetitive Transcranial Magnetic Stimulation for Achalasia.
Official title: To Investigate the Clinical Efficacy of Optical 3D Navigation Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Achalasia, Optimize the Treatment Parameters, and Provide a Noninvasive Treatment Strategy for Achalasia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Esophageal Achalasia
Transcranial Magnetic Stimulation, Repetitive
Vagus Nerve Motor Disorder
Functional Magnetic Resonance Imaging
Keywords: Achalasia
rTMS
fMRI
Non-invasive
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2023-09-07
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In patients with achalasia diagnosed by clinical symptoms, HREM and barium meal examination, functional connectivity analysis of DMV with three brain regions (precentral gyrus, postcentral gyrus and insula) was performed by scanning T1 structural magnetic resonance imaging, and brain regions with the strongest positive functional connectivity with DMV were selected as individualized rTMS targets by optical 3D navigation. All patients were randomly divided into four groups: sham-rTMS group, 5Hz-rTMS group, 10Hz-rTMS group, and 30Hz-rTMS group, and each group received acute and chronic stimulation, respectively.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to investigate the clinical efficacy of repetitive transcranial magnetic stimulation in the treatment of achalasia in patients diagnosed with achalasia by comprehensive evaluation of clinical symptoms, HREM, and barium meal examination, optimize rTMS treatment parameters, and provide an effective and noninvasive new treatment strategy for achalasia. The main questions it aims to answer are:

1. To investigate the clinical efficacy of individualized treatment of achalasia with optical 3D navigation repetitive transcranial magnetic stimulation.
2. Optimize rTMS parameters to achieve the best clinical treatment.

Participants will need to fill out the Eckardt score scale and SF-36 quality of life scale, undergo cranial T1 structural magnetic resonance for functional connectivity analysis, and select the brain region with the strongest positive functional connectivity to the DMV as the rTMS target. All patients were randomly divided into four groups: sham-rTMS group, 5Hz-rTMS group, 10Hz-rTMS group, and 30Hz-rTMS group, and each group received acute and chronic stimulation, respectively. In the acute stimulation stage, patients only need to do rTMS once, and HREM and HRV detection are given before and after rTMS (stimulation for 1s, interval for 4s, 10 pulses per second, receiving a total of 3000 pulses); in the chronic stimulation stage, patients receive 25 minutes of rTMS actual stimulation or sham stimulation each time, lasting for 20 times, which is completed within 30 days, and the actual stimulation parameters are the same as those of acute stimulation, and the sham stimulation coil is consistent with the appearance and sound of proper stimulation, but there is no substantial stimulation. High-definition esophageal manometry, timed barium meal, heart rate coefficient of variation, and serum neurotransmitters were performed before and after chronic stimulation. Finally, a weekly telephone follow-up was performed for 12 weeks, including Eckardt score and SF-36 quality of life scale.

Detailed description: Study hypothesis: By analyzing the strongest resting-state functional connectivity between DMV and right precentral gyrus, left postcentral gyrus, and left brain leads in achalasia patients, individualized rTMS treatment with optical 3D navigation was applied to relax LES and relieve the clinical symptoms of dysphagia.

Statistical methods: SPSS 25.0 software was used to process the data, symptom score, manometry parameters, serum transmitters and other quantitative indicators. If they met the normal distribution, they were expressed as Mean ± SD. The t-test was performed for the comparison between the two groups; if they did not obey the normal distribution, the median (quartile) was used for statistical description. The rank sum test was used for the comparison between the two groups. Enumeration data were described using number of cases (percentage), and X2 test, corrected X2 test, or Fisher exact test were performed for comparison between the 2 groups.

Eligibility criteria: Inclusion Criteria:

* Aged more than 18 years old, less than 75 years old;
* Clinical symptoms evaluation, HREM, esophageal barium meal examination confirmed the diagnosis of achalasia;
* Willing to sign informed consent.

Exclusion Criteria:

* Presence of metal hardware in close contact with the discharge coil (e.g., cochlear implant, internal pulse generator, or drug pump). Note: Cochlear implants include electrodes, magnets, loop antennas, and electronic chips under the scalp implanted in the cochlea;
* Intracranial metal implants;
* Patients with cardiac pacemakers, vagal nerve stimulation (VNS) systems, spinal cord stimulators, and deep brain stimulation implanted with pulse generators should be used with caution;
* People at higher risk of noisy hearing loss and patients with hypoacusis symptoms should be used with caution;
* Pregnancy;
* Severe or recent heart disease;
* Personal history of epilepsy, use of known drugs that lower the seizure threshold, and other factors that may lower the seizure threshold (e.g., lack of sleep, infection, and alcohol abuse);
* Increased intracranial pressure;
* Acute phase of intracranial infection and hemorrhagic disease;
* Contraindications to MRI examination or claustrophobia;
* Refusal to sign informed consent.

Primary outcomes:
measure: Eckardt score
timeFrame: Measured immediately after intervention.
measure: Real-time esophageal barium meal examination
timeFrame: Measured immediately after intervention.
measure: High-resolution esophageal manometry（HREM）
timeFrame: Measured immediately after intervention.
Secondary outcomes:
measure: Heart rate variability assessment
timeFrame: Measured immediately after intervention.
measure: Neurotransmitter detection analysis
timeFrame: Measured immediately after intervention.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
Study officials:
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