A Positron Emission Topographic (PET) Study on Depression Patient With Electroacupuncture

Study Overview
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Brief Summary
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This is a randomized, assessor-blind, placebo controlled study in major depressive disorder (MDD) patients. Subjects receiving antidepressant drug (FLX) would be assigned to receive either 18 sham / active DCEAS for in 6 weeks. Changes in the severity of depressive symptoms over time are measured using depression rating scales. Brain glucose metabolic levels are measured using PET at baseline and endpoint. The most intriguing and expected result might be that acupuncture treated-patients may display comparable or even better outcomes and the clinical improvements by acupuncture are correlated with the restoration of the activities in the related brain regions.

Detailed Description
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Although the development of various classes of antidepressant drugs, represented by selective serotonin reuptake inhibitors (SSRI), has considerably improved the prognosis and the tolerability in the treatment of depressive disorders, the currently available antidepressant therapy is still incomplete, because there are about 40% of depressed individuals who cannot obtain full response and a large proportion of the patients experience recurrent episodes. Recently the principal investigator has completed a clinical trial to test whether dense cranial electroacupuncture stimulation (DCEAS) could enhance the antidepressant efficacy in the early phase of SSRI treatment (fluoxetine, FLX) of major depressive disorder (MDD). It was found that DCEAS is clinically safe and effective in augmenting the antidepressant efficacy in early SSRI treatment. As we hypothesize that this normalizing effect is associated with the modulation of various nervous functions associated with the pathophysiology of MDD, we design this neuroimaging (PET) DCEAS study to delineate the related mechanisms. The objective of this study are: 1) To compare clinical improvements on depressive symptoms between DCEAS and FLX monotherapy in MDD subjects; (2) To determine the effects of DCEAS treatment on glucose metabolic levels in related brain regions in comparison with healthy controls and FLX-treated patients, using PET scanning; and (3) To correlate between clinical improvements and changes in PET-measured activities of related brain regions in a pool of the subjects treated with DCEAS and FLX. In this 6-week, assessor-blind, randomized, controlled study of DCEAS as additional treatment with the antidepressant drug FLX, a total of 82 patients with major depressive disorder (MDD) will be recruited. The patients will be randomly assigned to FLX (10-30 mg/day) combined with sham (n =41) or FLX with active DCEAS (n =41) (18 sessions, 3 sessions a week). Changes in the severity of depressive symptoms over time are measured using depressive instruments. Clinical response and remission rates are also calculated. Two sessions of PET scan will be conducted at baseline and endpoint. The study will be conducted at HKU School of Chinese Medicine, Queen Mary Hospital, and Kowloon Hospital, Hong Kong.

Official Title
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The Identification of Central Neural Network for Antidepressant Effects of Dense Cranial Electroacupuncture Stimulation - a Positron Emission Topographic (PET) Study

Conditions
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Major Depressive Disorder, Depression

Intervention / Treatment
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* Drug: Fluoxetine
* Procedure: DCEAS (Hwato®/ Dongbang®)
* Procedure: n-CEA (Strietberger®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: with righthandedness; have first-episode MDD diagnosed as the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); and HAMD-17 score is ≥ 20; and never had any psychoactive medications. Exclusion Criteria: unstable medical conditions; have suicidal ideas or attempts or aggressive behavior; previously experienced manic, hypomanic, or mixed episode; immediate family members have bipolar or psychotic disorders; treatment with investigational drugs in past 6 months; alcoholism or drug abuse in past 1 year; or have needle phobia.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DCEAS<br>Dense cranial electroacupuncture stimulation (DCEAS) For those who were currently under antidepressant treatment, they would continue the existing treatment regimens. For those who were not medicated at the time of trial, fluoxetine (FLX) was given at an initiate dose of 10 mg/day and escalated to an optimal dose within one week, based on individual response, but the maximum dose was set at 40 mg/day. | Drug: Fluoxetine<br>* Subjects of both study arms received orally administered SSRIs for 4 weeks in an open manner. For those who were currently under antidepressant treatment, they would continue the existing treatment regimens. For those who were not medicated at the time of trial, fluoxetine (FLX) was given at an initiate dose of 10 mg/day and escalated to an optimal dose within one week, based on individual response, but the maximum dose was set at 40 mg/day.<br>* Other names: Fluxen;Procedure: DCEAS (Hwato®/ Dongbang®)<br>* Six pairs of cranial acupoints are used: Baihui (Du-20) and Yintang (EX-HN3), left Sishencong (EX-HN1) and Toulinqi (GB15), right Sishencong (EX-HN1) and Toulinqi (GB15), bilateral Shuaigu (GB8), bilateral Taiyang (EX-HN5), and bilateral Touwei (ST8). All these acupoints are located on the forehead. Disposable acupuncture needles (Hwato®/ Dongbang®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm obliquely into acupoints, on which low- and high-frequency alternating electrical stimulation with continuous waves is conducted for 30 min. The intensity is adjusted to a level at which patients feel comfortable.<br>* Other names: Dongbang®;|
| Sham Comparator: n-CEA<br>Non-invasive cranial electroacupuncture (n-CEA) For those who were currently under antidepressant treatment, they would continue the existing treatment regimens. For those who were not medicated at the time of trial, fluoxetine (FLX) was given at an initiate dose of 10 mg/day and escalated to an optimal dose within one week, based on individual response, but the maximum dose was set at 40 mg/day. | Drug: Fluoxetine<br>* Subjects of both study arms received orally administered SSRIs for 4 weeks in an open manner. For those who were currently under antidepressant treatment, they would continue the existing treatment regimens. For those who were not medicated at the time of trial, fluoxetine (FLX) was given at an initiate dose of 10 mg/day and escalated to an optimal dose within one week, based on individual response, but the maximum dose was set at 40 mg/day.<br>* Other names: Fluxen;Procedure: n-CEA (Strietberger®)<br>* Streitberger's acupuncture needles will be applied on the same acupoints, with the same electrical stimulation parameters, except that the needles only adhere to the skin instead of insertion.<br>* Other names: Strietberger®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAMD-17 | Depression symptoms is measured using the 17-item Hamilton Depression Scale. Assessments will be conducted at baseline and once weekly thereafter. | 42-day (course of treatment) | 
| SDS | Depression symptoms is measured using the Self-Rating Depression Scale (SDS). Assessments will be conducted at baseline and once weekly thereafter. | 42-day (course of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET scanning | The secondary outcome measure of high interest is the results of PET scanning. Two sessions of PET scan will be conducted at baseline and endpoint for enrolled subjects. An additional group of age- and gender-matched healthy subjects will be invited for one-session PET scan. | 42-day (course of treatment) | 
| Clinical response | Clinical response, defined as greater than or equal to 50% reduction at endpoint from baseline on HAMD-17, is measured at the baseline and once weekly thereafter. | 42-day (course of treatment) | 
| Remission | Remission, defined as 7 points or less on HAMD-17 score, is measured at the baseline and once weekly thereafter. | 42-day (course of treatment) | 
| Latency | The latency of the clinical response. | 42-day (course of treatment) | 
| Adverse events | Adverse events are assessed using the Treatment Emergent Symptom Scale (TESS) when applicable. | 42-day (course of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depressive Disorder, Depressive Symptoms, Depressive Syndrome, Emotional Depression