The Efficacy and Cerebral Mechanism of Intradermal Acupuncture for Major Depressive Disorder

Sponsor

Xiaomei Shao (Other)

Overall Status

Recruiting

CT.gov ID

NCT05720637

Collaborator

Zhejiang Provincial Tongde Hospital (Other), First People's Hospital of Hangzhou (Other), The First Affiliated Hospital of Zhejiang Chinese Medical University (Other)

120

Enrollment

Location

Arms

37.9

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Major depressive disorder (MDD) is highly prevalent, affecting nearly 4% of the global population. Pharmacotherapy is the frontline treatment recommended by the guideline, but it also has some limitations such as delayed onset, inadequate response, and drug resistance. Intradermal acupuncture (IA) is a method of using short indwelling needles retained under the skin to produce continuous stimulation for long-term efficacy. It has been reported that IA combination medication appears to be more valuable than medication alone in the treatment of MDD, however, there is a lack of high-quality clinical evidence.While several studies have proposed that manual or electroacupuncture can improve MDD symptoms by modulating brain networks, the cerebral mechanism of IA as superficial acupuncture for MDD has not been reported. Hence, we designed a multicentre randomized controlled trial to assess the clinical efficacy and safety of IA for MDD and preliminarily explore the potential therapeutic mechanisms for IA by functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: SSRI Device: SIA Device: AIA	N/A

Detailed Description

A total of 120 patients with MDD who meet the inclusion criteria will be included in the study. Participants will be randomly assigned 1:1:1 to the waiting list group (patients in this group will be treated with selective 5-hydroxytryptamine reuptake inhibitors (SSRIs) only), sham intradermal acupuncture combined with SSRIs (SIA) group and active intradermal acupuncture combined with SSRIs (AIA) group. The study will assess the efficacy and safety of intradermal acupuncture for MDD. In addition, we will explore the possible cerebral mechanisms by which IA exerts its antidepressant effects.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Efficacy and Cerebral Mechanism of Intradermal Acupuncture for Major Depressive Disorder: a Study Protocol for a Randomized Controlled Trial

Actual Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Dec 30, 2025

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Waiting list group This group will include 40 patients with MDD who will be treated with oral SSRIs only, the dosage of which will be determined by the psychiatrist. At the end of this trial, patients could choose 6 weeks' intradermal acupuncture treatments free of charge.	Drug: SSRI SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial. Other Names: selective 5-hydroxytryptamine reuptake inhibitor
Sham Comparator: SIA group This group will include 40 patients with MDD who will be treated with sham intradermal acupuncture (SIA) combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.	Drug: SSRI SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial. Other Names: selective 5-hydroxytryptamine reuptake inhibitor Device: SIA This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). The SIA will use the same size, colour and material as the AIA with a thin silicone pad in the middle instead of the needle body. SIA will be attached to the acupoints and retained for 72 hours, removed and rested for one day. A total of 10 sessions will be performed over a period of 6 weeks. Other Names: sham intradermal acupuncture
Experimental: AIA group This group will include 40 patients with MDD who will be treated with active intradermal acupuncture (AIA) combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.	Drug: SSRI SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial. Other Names: selective 5-hydroxytryptamine reuptake inhibitor Device: AIA This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). Depending on acupoints' location, a φ0.201.5mm or φ0.201.2mm AIA will be selected. Press the AIA to insert it vertically into the acupoint and retain it in the skin. AIA will be retained for 72 hours with a day's rest after removal. During the period of needle retention, participants will be instructed to press the AIA 3-4 times a day for approximately 1 minute each time, with as much stimulation as the patient can tolerate, at intervals of approximately 4 hours. A total of 10 sessions will be performed over a period of 6 weeks. Other Names: active intradermal acupuncture

Arm

Intervention/Treatment

Other: Waiting list group

This group will include 40 patients with MDD who will be treated with oral SSRIs only, the dosage of which will be determined by the psychiatrist. At the end of this trial, patients could choose 6 weeks' intradermal acupuncture treatments free of charge.

Drug: SSRI

SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial.

Other Names:

selective 5-hydroxytryptamine reuptake inhibitor

Sham Comparator: SIA group

This group will include 40 patients with MDD who will be treated with sham intradermal acupuncture (SIA) combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.

Drug: SSRI

SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial.

Other Names:

selective 5-hydroxytryptamine reuptake inhibitor

Device: SIA

This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). The SIA will use the same size, colour and material as the AIA with a thin silicone pad in the middle instead of the needle body. SIA will be attached to the acupoints and retained for 72 hours, removed and rested for one day. A total of 10 sessions will be performed over a period of 6 weeks.

Other Names:

sham intradermal acupuncture

Experimental: AIA group

This group will include 40 patients with MDD who will be treated with active intradermal acupuncture (AIA) combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.

Drug: SSRI

SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for the duration of the trial.

Other Names:

selective 5-hydroxytryptamine reuptake inhibitor

Device: AIA

This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). Depending on acupoints' location, a φ0.20*1.5mm or φ0.20*1.2mm AIA will be selected. Press the AIA to insert it vertically into the acupoint and retain it in the skin. AIA will be retained for 72 hours with a day's rest after removal. During the period of needle retention, participants will be instructed to press the AIA 3-4 times a day for approximately 1 minute each time, with as much stimulation as the patient can tolerate, at intervals of approximately 4 hours. A total of 10 sessions will be performed over a period of 6 weeks.

Other Names:

active intradermal acupuncture

Outcome Measures

Primary Outcome Measures

Changes in the Hamilton Depression Scale-17 (HAMD-17) Scores [Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up.]
The HAMD scale is the most commonly used in the clinical assessment of depression, including 17 items. The higher the score, the more severe the depression. 0-7 means no depressive symptoms, 8-17 means mild depression, 18-24 was divided into moderate depression, and 25-52 was divided into severe depression.

Secondary Outcome Measures

Changes in the Self-Rating Depression Scale (SDS) Scores [Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up.]
The standard score is the total of all scores multiplied by 1.25 to the nearest whole number on this scale, which has 20 questions. A standard score below 50 is normal; 50-60 is mild depression; 61-70 is moderate depression; 70 or more is severe depression.
Changes in the Pittsburgh Sleep Quality Index (PSQI) Scores [Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up]
The PSQI is used to assess the sleep quality of the participant in the last 1 month and consisted of 19 self-rated and 5 other rated items. The higher the score, the worse the sleep quality. Sleep quality is divided into 4 levels according to the total score.

Other Outcome Measures

Magnetic resonance imaging (MRI) data acquisition [Baseline, 6 weeks after treatment]
Brain MRI will be taken by a 3.0T MRI scanner to analyze the activity function of depressed patients' brain regions, such as the amygdala and hippocampus, before and after the intervention.
Magnetic resonance spectroscopy (MRS ) data acquisition [Baseline, 6 weeks after treatment]
MRS will be taken by a 3.0T MRI scanner to detect neurometabolic changes in depressed patients' brain regions, particularly the amygdala, before and after the intervention.
Blood samples biobank establishment [Baseline, 6 weeks after treatment]
blood samples will be collected to establish a blood sample bank and serum 5-HT levels will be tested.
Evaluation of acupuncture compliance [6 weeks after treatment]
At the end of the acupuncture intervention (end of week 6), compliance will be evaluated with the formula: Compliance Rate = (actual treatment times/total treatment times) *100%.
Adverse Events [Up to 10 weeks]
Adverse events such as bleeding, haematoma, or unbearable pain caused by the needle, as well as drug-induced nausea, vomiting or dizziness, will all be recorded.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed with MDD according to the International Classification of Disease-10 (ICD-10);
Aged between 18 and 60 years (no limitation on gender);
Administration of SSRIs;
Patients undergoing MRI and MRS should be right-handed and free of traumatic brain injury, claustrophobia or metal implants;
Written informed consent is obtained by the person or guardian.

Exclusion Criteria:

ICD-10 diagnoses: schizophrenia, bipolar disorder, manic episode or other psychotic disorders; alcohol and drug addiction;
Significant skin lesions, severe allergic diseases, tumors, and severe or unstable internal diseases involving the cardiovascular, digestive, endocrine, or hematological system;
Acute suicidal tendency;
Allergy to adhesive tape and fear of intradermal acupuncture;
Pregnancy and lactation;
Mental retardation and difficulty cooperating with doctors.
Participating in other clinical trials.