Effects of Nutrients Supplementation in Antidepressant Treated Depressive Disorder Patients

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled to evaluate the potential role of nutrients supplementation (LF chocolate /Erinacine A-enriched Hericium Erinaceus chocolate) on the therapeutic efficacy of antidepressants in major depressive disorder(MDD). 120 subjects who meet all the inclusion and exclusion criteria will be randomized into three categories, receiving 3 pieces of supplement nutrients-added or plain chocolates per day for a period of 24 weeks in total. The three categories are as follow: LF chocolate Erinacine A-enriched Hericium Erinaceus chocolate Plain chocolate without any supplementary nutrients added (placebo group) These MDD patients will continue their antidepressant regimen throughout the study. Symptom rating, blood samples for antidepressant-related/depressive disorder-related genome profiles identification, as well as for biomarkers assessment for metabolic indices, questionnaires and tests for psychosocial variables identification and patient's cognitive and social cognitive function or performance determination, will be carried out before and at certain time points within the 24-week tracking period. Patient's fecal samples will be acquired to recognize and to distinguish the alterations of these MDD patients microbiota profiles over the 24-week period.

Detailed Description
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Major depressive disorder (MDD) is a common, severe, and often life-threatening illness that involves the body, mood, and thoughts. Recent reports suggested that immune dysfunction could be linked with cognitive impairment and metabolic comorbidities, and accumulating evidence suggested that the regulation of the microbiota- gut-brain axis has been shown to impact inflammation and to affect brain function. This randomized, double-blind, placebo-controlled is to evaluate the potential role of nutrients supplementation (LF chocolate /Erinacine A-enriched Hericium Erinaceus chocolate) on the therapeutic efficacy of antidepressants in major depressive disorder(MDD). 120 MDD outpatients (aged 20-70 years) from the National Cheng Kung University Hospital who meet the Diagnostic and Statistical Manual of mental disorders, Fifth Edition (DSM-5) and Hamilton Rating Scale for Depression (HAMD) scores ≥ 7, receiving fluoxetine or venlafaxine so as SSRI or SNRI antidepressants will be enrolled. Subjects who meet all the inclusion and exclusion criteria will be randomized into three categories, with 40 subjects each, receiving 3 pieces of supplement nutrients-added or plain chocolates (placebo) manufactured by GRAPE KING BIO LTD per day for a period of 24 weeks in total. The three categories are as follow: LF chocolate Erinacine A-enriched Hericium Erinaceus chocolate Plain chocolate without any supplementary nutrients added (placebo group) These MDD patients will continue their antidepressant regimen throughout the study. Follow-up visits will be arranged at week no. 0, 2, 4, 8, 12, 16, 20 and 24, in which week no. 0, 4, 12 and 24 will be the four most important re-visit timing. Various assessments or tests will be arranged in these 24-week period. Symptom rating with 17-item Hamilton Rating Scale for Depression (HAM-D) by psychiatrist will be done at every visits. Blood samples for antidepressant-related/depressive disorder-related genome profiles identification, as well as for biomarkers assessment for metabolic indices, will be obtained at week no. 0, 4, 12 and 24. Questionnaires aimed for psychosocial variables (environmental factors) identification including social support scales (SSS), quality of life scale (QOLs) and Recent life changes questionnaire (RCLQ) will be self-answered by patients. Continuous Performance Test (CPT), finger-Tapping Test (FPT) and Wisconsin Card Sorting Test (WCST) will be utilized to evaluate their cognitive performance. Mayer-Salovey-Caruso emotional Intelligent Test (MSCEIT) will help in social cognitive function assessment. Patient's fecal samples will be acquired at week no. 0, 4, 12 and 24 to recognize and to distinguish the alterations in MDD patients microbiota profiles.

Official Title
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Effects of Nutrients Supplementation in Antidepressant Treated Depressive Disorder Patients

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Dietary Supplement: LF/Erinacine A-enriched Hericium/Plain chocolate + antidepressant(s)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depressive disorder (MDD) outpatients meet DSM- criteria Hamilton Rating Scale for Depression (HAM-D) ≥ 7 Start to receive fluoxetine or venlafaxine or those who have received the SSRI or SNRI antidepressants Exclusion Criteria: (A) had DSM-5 diagnosis for substance abuse within the past three months; (B) had taken monoamine oxidase inhibitors; (C) had an organic mental disorder, mental retardation, dementia, or other diagnosed neurological illness; (D) had a surgical condition or a major physical illness; (E) pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LF chocolate + antidepressant(s)<br>Participants with LF chocolate add-on to their antidepressants regimen. | Dietary Supplement: LF/Erinacine A-enriched Hericium/Plain chocolate + antidepressant(s)<br>* 3 pieces per day<br>|
| Active Comparator: Erinacine A-enriched Hericium chocolate + antidepressant(s)<br>Participants with Erinacine A-enriched Hericium chocolate add-on to their antidepressants regimen. | Dietary Supplement: LF/Erinacine A-enriched Hericium/Plain chocolate + antidepressant(s)<br>* 3 pieces per day<br>|
| Placebo Comparator: Plain chocolate + antidepressant(s)<br>Participants with plain chocolate add-on to their antidepressants regimen. | Dietary Supplement: LF/Erinacine A-enriched Hericium/Plain chocolate + antidepressant(s)<br>* 3 pieces per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in participant's Hamilton Rating Scale for Depression (HAM-D) score | Depressive symptom rating; 21 items int total, eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe, while nine are scored from 0-2; [higher scores denote worse symptoms/signs of depression] | week no. 0, 2, 4, 8, 12, 16, 20, 24 | 
| Change in participant's BW(kg), Height(cm), Waist circumference(cm), BMI (kg/m2) | Metabolic indices; BW (to the nearest 0.1 kg), height (to the nearest 0.1 cm), and waist circumference (to the nearest 0.1 cm), weight and height will be combined to report BMI in kg/m^2 | week no. 0, 2, 4, 8, 12, 16, 20, 24 | 
| Change in participant's Glucose profiles | Metabolic indices; HbA1c(%)+Fasting plasma glucose (mg/dl)+Fasting serum insulin concentrations (uIU/ml)+Homeostasis model assessment-estimated insulin resistance (HOMA-IR) index+Homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) {HOMA- IR= [fasting plasma insulin level (uIn/ml)*fasting plasma glucose level (mg/dl)/405]; HOMA- IR ≥2.5 => Insulin resistance (+)} {HOMA-β= (360× fasting serum insulin [uIn/ml]) / (fasting plasma glucose [mg/dL] -63)} | week no. 0, 4, 12, 24 | 
| Change in participant's Fasting serum leptin level (ng/mL) | Metabolic indices | week no. 0, 4, 12, 24 | 
| Change in participant's Fasting serum lipid profiles | Metabolic indices; including Fasting total cholesterol(mg/dL), High density lipoprotein (HDL) cholesterol(mg/dL), Low-density lipoprotein (LDL) cholesterol(mg/dL), Triglyceride (TG) concentration(mg/dL) | week no. 0, 4, 12, 24 | 
| Change in participant's Cortisol(ug/dL) level | Metabolic indices | week no. 0, 4, 12, 24 | 
| Change in participant's C-peptide(ng/dL) | Metabolic indices | week no. 0, 4, 12, 24 | 
| Change in participant's Inflammatory cytokines levels | Metabolic indices; Fasting plasma C-reactive protein (CRP) level (pg/mL) + Oxytocin(pg/mL) + Leptin(mg/mL) | week no. 0, 4, 12, 24 | 
| Change in participants's Quality of life scale (QOLs) scores [WHOQOL-BREF] | Psychosocial variables as environment factors; Quality of Life Scale developed through the World Health Organization (WHOQOL-BREF) & Health-Related Quality of Life (HRQOL) questionnaires will be used as assessment tools WHOQOL-BREF: 4 domains will be assessed, consists of 1. Physical Health 2. Psychological 3. Social Relationship 4. Environment; [higher scores in each domains denote higher quality of life] | week no. 0, 4, 12, 24 | 
| Change in participants's Quality of life scale (QOLs) scores [HRQOL] | Psychosocial variables as environment factors; Quality of Life Scale developed through the World Health Organization (WHOQOL-BREF) & Health-Related Quality of Life (HRQOL) questionnaires will be used as assessment tools HRQOL: 4 domains will be assessed, consists of 1. Physical Health 2. Psychological 3. Level of independence 4. Social Relationship [higher scores in each domains denote higher quality of life] | week no. 0, 4, 12, 24 | 
| Change in participant's Cognitive performance | Continuous Performance Test (CPT)[visual information processing & attentive capacity], Finger Tapping Test (FPT), Wisconsin Card-Sorting Test (WCST) | week no. 0, 12, 24 | 
| Change in participant's Social cognitive functional performance | Mayer-Salovey-Caruso emotional Intelligence Test (MSCEIT) scores; perceiving + facilitating + understanding + managing emotion | week no. 0, 12, 24 | 
| Change in participant's Microbiota profiles | Fecal samples; Types of microorganisms + no. of colonies (colony-forming unit, CFU) | week no. 0, 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major depressive disorder, Supplement nutrients, Antidepressants