Escitalopram Plus PS128 vs. Escitalopram

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of escitalopram plus PS128 to escitalopram in the acute treatment of patients with major depressive disorder.

Detailed Description
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In this 6-week, double-blind, fixed-dose study, patients with major depressive disorder are randomly assigned to escitalopram (10 mg daily) plus PS128 (a psychobiotic) (300 mg two times daily, equivalent to 3 ×1010 CFU two times daily) or escitalopram (10 mg daily) groups. The rating scales and instrument, including Clinical Global Impression-Severity, 17-item Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, Global Assessment of Functioning, Heart Rate Variability, Depression and Somatic Symptoms Scale, Work and Social Adjustment Scale, Short form 36 and Pittsburgh Sleep Quality Index, are used to measure treatment outcomes at weeks 0, 1, 2, 3, 4, 5, and 6. UKU Side Effect Rating Scale and Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome are used to measure side effects. Generalized estimating equations model will be used to analyze the differences between two groups with respect to efficacy and safety measures on time after adjusting for baseline severity, sex, age and age at onset of illness.

Official Title
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A Randomized, Double-blind, Comparison of the Efficacy and Safety of Escitalopram Plus PS128 to Escitalopram in the Acute Treatment of Patients With Major Depressive Disorder

Conditions
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Major Depression

Intervention / Treatment
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* Dietary Supplement: Lactobacillus plantarum PS128


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depressive disorder CGI >=4 the score of the 17-item Hamilton Rating Scale for Depression (HAMD-17) was 18 or higher. washout of antipsychotics at least 3 days written informed consents Not taking fluoxetine at least one month before admission. Exclusion Criteria: History of schizophrenia, schizoaffective disorder or organic mental disorders. comorbid with substance abuse/dependence in the past 6 months. with psychotic features treatment-resistant depression or receiving electroconvulsive therapy. History of serious adverse events to escitalopram female subjects with pregnancy or lactation. severe physical illness receiving antibiotics treatment in the past two weeks. taking products with probiotics.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Experimental: escitalopram plus128<br>escitalopram (10 mg daily) plus PS128(a psychobiotic) (300 mg two times daily, equivalent to 3 ×1010 CFU two times daily) | Dietary Supplement: Lactobacillus plantarum PS128<br>* 10 mg qd of escitalopram qd plus 300mg bid of Lactobacillus plantarum PS128 to enhance antidepressive effect<br>|
| Active Comparator: escitalopram<br>10 mg/d of escitalopram | Dietary Supplement: Lactobacillus plantarum PS128<br>* 10 mg qd of escitalopram qd plus 300mg bid of Lactobacillus plantarum PS128 to enhance antidepressive effect<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression severity by the change of 17-item Hamilton Rating Scale for Depression (HAMD-17) total scores | 17-item Hamilton Rating Scale for Depression (HAMD-17) is widely used in clinical setting to evaluate depression symptoms in the past week. Higher total HAMD-17 scores (ranging from 0 to 52) indicate more severe depression. | Time Frame: The HAMD-17 was rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical severity by Clinical Global Impression-Severity (CGI-S) | The CGI was developed for use in NIMH-sponsored clinical trials to provide a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. The CGI comprises one-item measures evaluating the severity of psychopathology from 1 to 7 and higher scores indicate higher severity. | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| Assessments of safety for general adverse events | General adverse events were evaluated by a standardized the UKU Side Effect Rating Scale. A score of 1, 2 or 3 on any UKU item that first occurred or worsened during treatment indicated adverse events cases. | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| Change of body weights | Body weights | Time Frame: Body weights were assessed at baseline and week 6(or on early termination). | 
| Change of body mass index (BMI) | body mass index (BMI) | Time Frame: BMI was assessed at baseline and week 6(or on early termination). | 
| Change of pulse rate | pulse rate | Time Frame: Pulse rates were checked at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination). | 
| Change of blood pressure | blood pressure (both systolic and diastolic) | Time Frame: Blood pressure were checked at baseline and at weeks 1, 2, 3, 4, and 6 (or on early termination). | 
| Change of ECG QT Interval | 12-lead electrocardiogram (ECG) ECG QT Interval. | Time Frame: ECG were assessed at baseline and week 6 (or on early termination). | 
| change of fasting glucose. | Laboratory tests including fasting glucose. | Time Frame: laboratory test mentioned above were assessed at baseline and week 6(or on early termination. | 
| change of liver function | Laboratory tests including alanine aminotransferase [ALT] and aspartate aminotransferase [AST]. | Time Frame: laboratory test mentioned above were assessed at baseline and week 6 (or on early termination). | 
| change of renal function | Laboratory tests including blood urea nitrogen [BUN], creatinine. | Time Frame: laboratory test mentioned above were assessed at baseline and week 6 (or on early termination). | 
| change of lipid profiles. | Laboratory tests including triglycerides, cholesterol, high density lipoprotein [HDL], and low density lipoprotein [LDL]. | Time Frame: laboratory test mentioned above were assessed at baseline and week 6(or on early termination). | 
| Assessments of quality of life | The Short-Form-36 (SF-36) is comprised of the physical component summary (PCS) which measures physical health, and the mental component summary (MCS) which measures mental health. PCS includes 4 subscales: 1) physical functioning, 2) role physical limitations, 3) body pain, 4) general health; MCS includes 4 subscales: 1) vitality, 2) social functioning, 3) role emotional limitations, and 4) mental health. SF-36 raw scores were processed according to the user manual to obtain standardized scores for all 8 SF-36 subscales, PCS and MCS. Scores for the SF-36 subscales range from 0 to 100, with a higher score representing better QOL. The PCS and MCS were standardized according to general population means and variances to produce scores with a common mean of 50 and standard deviation of 10 (T-scores). Thus, any score < 50 represents a reduction from normal health. | Time Frame: Medical Outcomes Study Short-Form 36 was assessed at baseline and week 6 | 
| Assessments of heart rate variability | Heart rate variability | Time Frame: Heart rate variability was assessed at baseline and week 6 | 
| depression and somatic symptoms evaluation | The Depression and Somatic Symptoms Scale (DSSS) is composed of a 12-item depression subscale (DS) and a ten-item somatic subscale (SS), which includes a five-item pain subscale (PS). Each item is scored from 0 to 3 (absent, mild, moderate, and severe) according to the severity of symptoms, with the total score ranging from 0 to 36 and 0-30 for the DS and the SS, respectively. Higher total score indicates more severe depression and somatic symptoms. | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| Gastrointestinal Symptoms evaluation | Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS) includes 15 questions on a scale of 1 to 7, depending on how inconvenient it had been during the previous week. A higher score indicates more inconvenient symptoms. Combination scores among 15 questions can assess the following five domains: reflux syndrome (heartburn and acid regurgitation), abdominal pain (stomach ache, gastric hunger pains and nausea), indigestion syndrome (gastric borborygmus, gastric bloating, eructation and increased flatus), diarrhea syndrome (diarrhea, loose stools and urgent need to defecate) and constipation syndrome (constipation, hard stools and feeling of incomplete evacuation). | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| Sleep Quality evaluation: The Pittsburgh Sleep Quality Index (PSQI) | The Pittsburgh Sleep Quality Index (PSQI) is a 19-item, self-rated questionnaire designed to measure sleep quality and disturbance over the past month in clinical populations. The 19 items are grouped into 7 components, including (1) sleep duration, (2) sleep disturbance, (3) sleep latency, (4) daytime dysfunction due to sleepiness, (5) sleep efficiency, (6) overall sleep quality, and (7) sleep medication use. Each of the sleep components yields a score ranging from 0 to 3, with 3 indicating the greatest dysfunction. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality. In distinguishing good and poor sleepers, a global PSQI score > 5 yields a sensitivity of 89.6% and a specificity of 86.5%. | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| Function evaluation | Global Assessment of Functioning (GAF) is used to rate severity of illness in psychiatry and covers the range from positive mental health to severe psychopathology. It is an overall (global) measure of how patients are doing Internationally, recording GAF is either done with a single value (this is the most severe of the symptom and functioning values) or both symptom (GAF-S) and functioning (GAF-F) values are recorded. The symptom and functioning scales have both 100 scoring possibilities (1-100). The 100-point scales are divided into 10 intervals, or sections, each with 10 scoring possibilities (examples: 31-40 and 51- 60). Verbal instructions (called anchor points) describe symptoms and functioning relevant for scoring in the 10-point intervals. | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 
| change of work and social adjustment | Work and Social Adjustment Scale(WSAS) is a widely used questionnaire by patients' perspectives concerning impaired functioning. The WSAS comprises 5 items (work, home management, social leisure, private leisure, and relationships; see Appendix A), each rated on a scale of 0 to 8, which can also be pooled (total score 0-40; higher scores denote more disability) | The scales were rated at baseline, and again at weeks 1, 2, 3, 4, 5 and 6 (or on early termination). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psychobiotics, major depressive disorder, escitalopram