Randomized Controlled Study of Optical 3D Navigated Repetitive Transcranial Magnetic Stimulation for Achalasia.

Sponsor

Zhang Nina (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06027190

Collaborator

(none)

112

Enrollment

Location

Arms

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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:

To investigate the clinical efficacy of individualized treatment of achalasia with optical 3D navigation repetitive transcranial magnetic stimulation.
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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Achalasia Transcranial Magnetic Stimulation, Repetitive Vagus Nerve Motor Disorder Functional Magnetic Resonance Imaging	Device: Repetitive transcranial magnetic stimulation Device: Sham	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham group Intervention Name and Specification: Placebo coil (Magstim Company, Whitland, UK): looks and sounds consistent with true coil but does not produce current stimulation.	Device: Sham Placebo coil (Magstim Company, Whitland, UK):
Experimental: rTMS group 5Hz-rTMS group 10Hz-rTMS group 30Hz-rTMS group Intervention Name and Specification: Transcranial magnetic stimulator (M-100 Ultimate, Yingzhi Technology Co., Ltd., China) 70 mm diameter figure-of-eight coil (BY90A, Yingzhi Technology Co., Ltd., China). Each group received acute and chronic stimulation, respectively. In the acute stimulation stage, patients only needed to do rTMS once, and HREM and HRV were administered before and after rTMS; in the chronic stimulation stage, patients received 25 minutes of rTMS true stimulation each time a day for 20 times, which was completed within 30 days, and the true stimulation parameters were the same as those of acute stimulation.	Device: Repetitive transcranial magnetic stimulation Intervention Name and Specification Transcranial magnetic stimulator (M-100 Ultimate, Yingzhi Technology Co., Ltd., China) . 70-mm-diameter figure-of-eight coil (BY90A, Yingzhi Technology Co., Ltd., China). 3) Placebo coil (Magstim Company, Whitland, UK): the appearance and sound were consistent with the true coil, but no current stimulation was produced.

Arm

Intervention/Treatment

Sham Comparator: Sham group

Intervention Name and Specification: Placebo coil (Magstim Company, Whitland, UK): looks and sounds consistent with true coil but does not produce current stimulation.

Device: Sham

Placebo coil (Magstim Company, Whitland, UK):

Experimental: rTMS group

5Hz-rTMS group 10Hz-rTMS group 30Hz-rTMS group Intervention Name and Specification: Transcranial magnetic stimulator (M-100 Ultimate, Yingzhi Technology Co., Ltd., China) 70 mm diameter figure-of-eight coil (BY90A, Yingzhi Technology Co., Ltd., China). Each group received acute and chronic stimulation, respectively. In the acute stimulation stage, patients only needed to do rTMS once, and HREM and HRV were administered before and after rTMS; in the chronic stimulation stage, patients received 25 minutes of rTMS true stimulation each time a day for 20 times, which was completed within 30 days, and the true stimulation parameters were the same as those of acute stimulation.

Device: Repetitive transcranial magnetic stimulation

Intervention Name and Specification Transcranial magnetic stimulator (M-100 Ultimate, Yingzhi Technology Co., Ltd., China) . 70-mm-diameter figure-of-eight coil (BY90A, Yingzhi Technology Co., Ltd., China). 3) Placebo coil (Magstim Company, Whitland, UK): the appearance and sound were consistent with the true coil, but no current stimulation was produced.

Outcome Measures

Primary Outcome Measures

Eckardt score [Measured immediately after intervention.]
Achalasia symptom score.
Real-time esophageal barium meal examination [Measured immediately after intervention.]
The severity of the patient 's condition and the therapeutic effect were evaluated by defining the height and maximum width of the residual barium area.
High-resolution esophageal manometry [Measured immediately after intervention.]
Esophageal motility evaluation criteria.

Secondary Outcome Measures

Heart rate variability assessment [Measured immediately after intervention.]
Dynamic electrocardiogram recording analysis of sympathetic vagal activity.
Neurotransmitter detection analysis [Measured immediately after intervention.]
Serum ACh, NO and VIP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

(1) Aged more than 18 years old, less than 75 years old; (2) Clinical symptoms evaluation, HREM, esophageal barium meal examination confirmed the diagnosis of achalasia; (3) Willing to sign informed consent.

Exclusion Criteria:

(1) 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; (2) Intracranial metal implants; (3) 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; (4) People at higher risk of noisy hearing loss and patients with hypoacusis symptoms should be used with caution; (5) Pregnancy; (6) Severe or recent heart disease; (7) 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); (8) Increased intracranial pressure; (9) Acute phase of intracranial infection and hemorrhagic disease; (10) Contraindications to MRI examination or claustrophobia; (11) Refusal to sign informed consent.