Effects and Central Mechanism of Electroacupuncture and MRI-navigated rTMS for PSD

Healthy Clinical Trial

Official title:

Effects and Central Mechanism of Electroacupuncture and MRI-navigated rTMS for PSD: a fMRI-based Single-center, Randomized, Controlled, Assessor-blinded Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05516680
• Other study ID #: 2022-LCYJ-PY-08
• Status: Recruiting
• Phase: N/A
• Start date: October 22, 2022
• Est. completion date: August 2025

Study information

• Verified date: August 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction:

Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life. Antidepressants are the first-line treatment for PSD, but many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture and rTMS have a positive effect on PSD. This trial aims to study the efficacy and safety of electro-acupuncture and a modern MRI-navigated rTMS for PSD and to explore its fMRI-based central mechanism on depression. It is hypothesized that electro-acupuncture and MRI-navigated rTMS treatment improves depressive symptoms, neuro-patho-physiological behaviors, quality of life and central response in PSD.

Methods:

In this randomized, controlled, assessors-blinded trial, sixty-four patients with PSD will be randomly allocated into the experiment group (n=32) or control group(n=32) . The experiment group will receive electro-acupuncture and MRI-navigated rTMS, and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, ten healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome is the change from baseline in the Hamilton Depression Scale-24 items (HAMD-24) scores at week 4. The primary analysis of central mechanism mainly involves cortical morphology, local spontaneous brain activity, and default mode network (DMN) functional connectivity based on fMRI at 0-wk and 4-wk. Secondary outcomes include the neuro-patho-physiological and quality of life changes in cortical excitability with motor evoked potential test(MEP), National Institutes of Health Stroke Scale(NIHSS), EuroQol Five Dimensions Questionnaire(EQ-5D) Scale, Modified Barthel Index(MBI) Scale and Short Form-Health Scale of Traditional Chinese Medicine(SF-HSTCM). Additional indicators include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess acceptability and economic practicality of the treatment in study. Outcomes are assessed at baseline and post intervention.

Discussion:

Electro-acupuncture and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and potential effect mechanism for the future use of electro-acupuncture and MRI-navigated rTMS for PSD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: August 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

Inclusion criteria for patients:

• Meet the TCM and Western medicine diagnostic criteria for first onset stroke within 6 months;

• Aged 40-75 years;

• Right-handed;

• Single infarct in basal ganglia (volume:3-5cm);

• Motor evoked potential (MEP) could be recorded by bilateral primary motor cortex (M1) stimulating.

• National Institutes of Health Stroke Scale (NIHSS) score <6;

• Hamilton Depression Scale-24 items (HAMD-24) score > 8;

• Clear consciousness, no hearing and visual impairment, and cooperative physical examination (Glasgow Coma Scale (GCS) score > 8);

• Complete the screening, and sign the informed consent form voluntarily.

Inclusion criteria for healthy subjects:

• Healthy subjects, aged 40-75 years;

• Right-handed;

• HAMD-24 score < 8;

• Sign the informed consent voluntarily.

Exclusion Criteria:

Exclusion criteria for patients:

• Have received other antidepressant therapy or involved in other clinical trials in 2 weeks;

• Infarct was located in the left DLPFC;

• With positive psychiatric history and major trauma exposure history, such as depression, epilepsy, etc. in the past;

• With other serious concomitant diseases (aphasia, severe edema, venous thrombosis, arteriosclerosis occlusion, diabetic vascular disease, peripheral neuropathy, spinal lesions, brain trauma, intracranial infection, brain tumors, etc.), and secondary diseases (heart, liver, renal failure, etc.);

• Infection around acupoints and/or intolerance of acupuncture manipulation;

• With MRI or rTMS contraindications (claustrophobia, metal implants, cochlear implants, impulsator, etc.).

Exclusion criteria for healthy subjects:

• Have involved in other clinical trials in 2 weeks;

• With positive psychiatric history and major trauma exposure history, including depression, epilepsy, etc. in the past;

• With MRI or rTMS contraindications (claustrophobia, metal implants, cochlear implants, impulsator, etc.).

Related Conditions & MeSH terms

• Depression
• Healthy
• Post-stroke Depression

Intervention

Device:
• electro-acupuncture
Acupoints consist of Neiguan (PC6, bilateral), Shuigou (GV26), Sanyinjiao (SP6, affected side), Yintang (EX-HN3), Shangxing (GV23), Baihui (GV20), and Sishencong (EX-HN1). Disposable stainless-steel needles (0.25mm× 40 mm)will be used. After skin disinfection, the acupuncturists will twist and thrust the needle handles to achieve the sensation of achiness, heaviness, and numbness (known as de qi) at all acupoints. Following needle manipulations, electroacupuncture instruments(SDZ-V) will be used to attached the needle handles at EX-HN3, GV23, GV20 and EX-HN1 with a dilatational wave of 5 ~ 10 Hz and a current intensity of 1 ~ 3 mA depending on the patient's tolerance. The needles will be removed after 30 minutes except for GV26 without needle retention. Participants will receive 12-20 electroacupuncture sessions over four weeks at a frequency of 3-5 times per week.
• MRI-navigated rTMS
MRI:All MRI scans were taken to acquire high-resolution T1-weighted anatomical images on the 3T MRI Scanner. Electromyography(EMG):Surface EMG was used to record MEPs from the abductor pollicis brevis for determining RMT of the non-lesioned motor cortex.A single TMS pulse was delivered to the location to identify the RMT,defined as the minimum intensity capable of evoking at least 5 MEPs of >50 µV in 10 consecutive trials.MRI-navigated rTMS:Using BrainSight system,left DLPFC targeting was individualized by reconstructing MRI data into a 3-dimensional brain image for neuro-navigation. Left DLPFC localization was central middle frontal gyrus,between superior frontal sulcus and middle frontal sulcus based on T1-weighted anatomical images.Focal rTMS was administered using a Magstim Rapid 2 connected to Y125-round coil that was identical.rTMS was applied at 110% RMT to the left DLPFC.At each session,3000 pulses were applied at 10 Hz with a total of 12-20 rTMS sessions over a 4-week period.

Locations

Country	Name	City	State
China	Drum Tower Hospital, Medical School of Nanjing University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acceptability Questionnaire	It is involved three levels: "fully accepted", "acceptable" and "not acceptable". The acceptance rate is calculated by the number of "fully accepted" and "acceptable" subjects. And higher rate mean a better outcome.	4 weeks
Other	Health Economics Evaluation	Cost-effectiveness analysis	4 weeks
Primary	Hamilton Depression Scale-24 items scores	Reduction rate	change from baseline to week 4
Primary	fMRI scan	Cortical morphology, local spontaneous brain activity, and default mode network (DMN) functional connectivity	0 week
Primary	fMRI scan	Cortical morphology, local spontaneous brain activity, and default mode network (DMN) functional connectivity	4 weeks
Secondary	motor evoked potential test	Cortical excitability	0 week
Secondary	motor evoked potential test	Cortical excitability	4 weeks
Secondary	National Institutes of Health Stroke Scale	The minimum and maximum values are 0 and 42 points, and higher scores mean a worse outcome.	0 week
Secondary	National Institutes of Health Stroke Scale	The minimum and maximum values are 0 and 42 points, and higher scores mean a worse outcome.	4 weeks
Secondary	EuroQol Five Dimensions Questionnaire Scale	The minimum and maximum values of utility index are -0.391 and 1 points, and higher scores mean a better outcome.	0 week
Secondary	EuroQol Five Dimensions Questionnaire Scale	The minimum and maximum values of utility index are -0.391 and 1 points, and higher scores mean a better outcome.	4 weeks
Secondary	Modified Barthel Index Scale	The minimum and maximum values are 0 and 100 points, and higher scores mean a better outcome.	0 week
Secondary	Modified Barthel Index Scale	The minimum and maximum values are 0 and 100 points, and higher scores mean a better outcome.	4 weeks
Secondary	Short Form-Health Scale of Traditional Chinese Medicine	The minimum and maximum values are 0 and 130 points, and higher scores mean a worse outcome.	0 week
Secondary	Short Form-Health Scale of Traditional Chinese Medicine	The minimum and maximum values are 0 and 130 points, and higher scores mean a worse outcome.	4 weeks