The Research Team Aims to Elucidate the Impact of ITBS (intermittent Theta Burst Stimulation) on the HPA Axis and Post-stroke Negative Emotions/depression by Conducting Human Experiments That Target Various Brain Regions.

Investigating the Impact of ITBS Stimulation on Various Brain Regions on the HPA Axis in Stroke Patients Using Resting-State EEG Data.

The project team will categorize stroke patients into three groups receiving iTBS stimulation targeting distinct brain regions: the cerebellum, the dorsolateral prefrontal cortex (DLPFC), and the primary motor cortex (M1), with 20 patients allocated to each group. Neurofunctional scores, anxiety and depression assessments, and transcranial magnetic stimulation evoked potentials (TEP) will be assessed pre- and post-treatment within each group. The relationship between anxiety and depression scores and brain network characteristics associated with emotions will be examined to investigate the impact of iTBS stimulation on post-stroke negative emotions. Furthermore, plasma and saliva samples will be collected from stroke patients in each group post iTBS intervention. ELISA will quantify ACTH levels in plasma and cortisol levels in both plasma and saliva, with the aim of exploring the effects of iTBS stimulation on the HPA axis across different brain regions.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Post-stroke Depression
• Intervention / Treatment: Device: iTBS

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Haotian Wu; Phone Number: +8617861172618; Email: 824918386@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Initial stroke onset <6 months, or the last stroke event occurred more than 6 months ago;
2. Age ≥18 years, <85 years (the likelihood of VCI increases beyond 85 years);
3. Patients with lesions in the middle cerebral artery region;
4. NIHSS >4, NIHSS <26;
5. mRS score ≥2;
6. Completion of CT or MRI;
7. No severe neurological or psychiatric disorders; no impairment of consciousness, able to cooperate with relevant treatments; no severe cognitive impairment (MMSE ≥15);
8. All participants are right-handed;
9. Signed informed consent form.

Exclusion Criteria:

1. History of epilepsy or psychiatric disorders (including depression, anxiety, or schizophrenia);
2. Severe comorbidities;
3. History of medication use: benzodiazepines, baclofen, or antidepressants;
4. Non-compliance with the protocol;
5. Acute phase of cerebral hemorrhage or acute infectious diseases;
6. Severe suicidal tendencies in patients with depression;
7. Severe headache, hypertension, malignant tumors, open wounds, vascular embolism, leukopenia, or other serious conditions;
8. Severe alcohol abuse;
9. History of cranial surgery or presence of metal implants in the brain;
10. Patients with cardiac pacemakers;
11. NIHSS > 26 or MMSE < 15;
12. Any condition likely to result in the patient's survival for less than 1 month;
13. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation of the cerebellar group using iTBS.; In the trial, the group is anticipated to enroll 20 patients with post-stroke balance dysfunction for iTBS cerebellar stimulation.At the outset of enrollment (T0 phase), peripheral blood and saliva samples must be obtained to assess HPA axis-related indicators and to evaluate brain networks using TMS. Following the 15-day treatment period (T1 phase), the aforementioned blood samples will be collected once more for further testing. Furthermore, any adverse events will be documented, encompassing secondary cardiovascular events, epilepsy, and mortality outcomes.	Device: iTBS; Sixty patients experiencing post-stroke negative emotions were recruited and categorized into groups based on their conditions. The group with post-stroke balance dysfunction underwent intermittent theta burst stimulation (iTBS) of the cerebellum, while the group with post-stroke cognitive dysfunction received iTBS stimulation of the left dorsolateral prefrontal cortex (DLPFC), and the group with post-stroke motor dysfunction underwent iTBS stimulation of the primary motor cortex (M1).The TMS stimulation protocol consisted of 20-minute sessions, five times a week, for a total of ten sessions, utilizing a figure-of-eight coil (model B9076, coil diameter 92 mm, manufactured by Yiruide Company in Wuhan, China, transcranial magnetic therapy device model NS5000). The stimulation intensity was set at 80% of the active motor threshold, with the coil positioned tangentially to the scalp and the handle oriented upwards.
Experimental: Stimulation of the Left Dorsolateral Prefrontal Cortex group using iTBS.; In the trial, the group is anticipated to enroll 20 patients with post-stroke balance dysfunction for iTBS Left Dorsolateral Prefrontal Cortex stimulation.At the outset of enrollment (T0 phase), peripheral blood and saliva samples must be obtained to assess HPA axis-related indicators and to evaluate brain networks using TMS. Following the 15-day treatment period (T1 phase), the aforementioned blood samples will be collected once more for further testing. Furthermore, any adverse events will be documented, encompassing secondary cardiovascular events, epilepsy, and mortality outcomes.	Device: iTBS; Sixty patients experiencing post-stroke negative emotions were recruited and categorized into groups based on their conditions. The group with post-stroke balance dysfunction underwent intermittent theta burst stimulation (iTBS) of the cerebellum, while the group with post-stroke cognitive dysfunction received iTBS stimulation of the left dorsolateral prefrontal cortex (DLPFC), and the group with post-stroke motor dysfunction underwent iTBS stimulation of the primary motor cortex (M1).The TMS stimulation protocol consisted of 20-minute sessions, five times a week, for a total of ten sessions, utilizing a figure-of-eight coil (model B9076, coil diameter 92 mm, manufactured by Yiruide Company in Wuhan, China, transcranial magnetic therapy device model NS5000). The stimulation intensity was set at 80% of the active motor threshold, with the coil positioned tangentially to the scalp and the handle oriented upwards.
Experimental: Stimulation of the Primary Motor Cortex (M1) group using iTBS.; In the trial, the group is anticipated to enroll 20 patients with post-stroke balance dysfunction for iTBS Primary Motor Cortex stimulation.At the outset of enrollment (T0 phase), peripheral blood and saliva samples must be obtained to assess HPA axis-related indicators and to evaluate brain networks using TMS. Following the 15-day treatment period (T1 phase), the aforementioned blood samples will be collected once more for further testing. Furthermore, any adverse events will be documented, encompassing secondary cardiovascular events, epilepsy, and mortality outcomes.	Device: iTBS; Sixty patients experiencing post-stroke negative emotions were recruited and categorized into groups based on their conditions. The group with post-stroke balance dysfunction underwent intermittent theta burst stimulation (iTBS) of the cerebellum, while the group with post-stroke cognitive dysfunction received iTBS stimulation of the left dorsolateral prefrontal cortex (DLPFC), and the group with post-stroke motor dysfunction underwent iTBS stimulation of the primary motor cortex (M1).The TMS stimulation protocol consisted of 20-minute sessions, five times a week, for a total of ten sessions, utilizing a figure-of-eight coil (model B9076, coil diameter 92 mm, manufactured by Yiruide Company in Wuhan, China, transcranial magnetic therapy device model NS5000). The stimulation intensity was set at 80% of the active motor threshold, with the coil positioned tangentially to the scalp and the handle oriented upwards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary Cortisol	Saliva samples were collected from stroke patients in each group post-iTBS intervention. These samples were analyzed using ELISA to quantify cortisol levels in saliva. The aim was to explore the impact of iTBS stimulation on various brain regions on the HPA axis. The concentration of cortisol in saliva is measured in nanograms per milliliter (ng/mL).	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Plasma adrenocorticotropic hormone	Plasma samples were collected from stroke patients in each group post-iTBS intervention. These samples were analyzed using ELISA to quantify ACTH levels in plasma. The aim was to explore the impact of iTBS stimulation on various brain regions on the HPA axis. The concentration of ACTH in plasma is measured in picograms per milliliter (pg/mL).	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Plasma cortisol	Plasma samples were collected from stroke patients in each group post-iTBS intervention. These samples were analyzed using ELISA to quantify cortisol levels in plasma. The aim was to explore the impact of iTBS stimulation on various brain regions on the HPA axis. The concentration of cortisol in plasma is measured in nanograms per milliliter (ng/mL).	From the patient's first treatment to the completion of the 14-day iTBS therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The National Institutes of Health Stroke Scale	The NIHSS ranges from 0 (no stroke symptoms) to 42 (most severe stroke), with higher scores indicating worse outcomes and lower scores indicating better outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.
The Modified Rankin Scale	The Modified Rankin Scale (mRS) ranges from 0 (no symptoms) to 6 (death), with higher scores indicating worse outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Hamilton Anxiety Scale	The Hamilton Anxiety Scale (HAM-A) ranges from 0 (no anxiety) to 56 (severe anxiety), with higher scores indicating worse outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Hamilton Depression Rating Scale	The Hamilton Depression Rating Scale (HDRS) ranges from 0 (no depression) to 52 (severe depression), with higher scores indicating worse outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Self-Rating Depression Scale	The Self-Rating Depression Scale (SDS) ranges from 20 (no depression) to 80 (severe depression), with higher scores indicating worse outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.
Self-Rating Anxiety Scale	The Self-Rating Anxiety Scale (SAS) ranges from 20 (no anxiety) to 80 (severe anxiety), with higher scores indicating worse outcomes.	From the patient's first treatment to the completion of the 14-day iTBS therapy.

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Kunming Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 28, 2025

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Behavioral Symptoms; Mood Disorders; Stroke; Depression; Depressive Disorder
• Other Study ID Numbers: Shen-PJ-Ke-2025-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No