A Pilot Study on Effect of add-on Sulforaphane to SSRIs and Application of Niacin Skin Flush Response Test in Major Depressive Disorder

Study Overview
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Brief Summary
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A 12-week, randomized controlled trial (RCT) will be conducted to explore the effect of add-on sulforaphane (SFN) to selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder (MDD). This study also aims to explore the value of niacin skin flush response test in MDD. One hundred adults diagnosed with MDD will be recruited. Then all the patients will be randomly assigned to SSRI only group and SSRI plus SFN group. Clinical symptoms and side-effects will be evaluated using the 17-Hamilton Depression Rating Scale (17-HDRS), the Hamilton Anxiety Scale (HAMA), Treatment Emergent Symptom Scale (TESS), and Asberg's Rating Scale for Side Effects (SERS) at baseline and weeks 2, 4, 8 and 12 after treatment. Fifty healthy subjects will be recruited as control group. For all subjects, testing of niacin skin flush response and serum levels of nuclear factor erythroid-2-related factor 2(Nrf-2), p-Nrf2, Heme Oxygenase-1 (HO-1), malondialdehyde (MDA) and erythrocyte glutathion peroxidase (GPX) will be performed at baseline and endpoint. The primary outcome is the reduction rate in 17-HDRS total score from baseline to the end of the study. The secondary outcomes include changes in niacin skin flush response test and levels of serum markers. All the data will be analyzed by SPSS software.

Official Title
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A Pilot Study on Effect of add-on Sulforaphane to SSRIs and Application of Niacin Skin Flush Response Test in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SSRIs
* Dietary Supplement: SSRI plus Sulforaphane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-60 years; diagnosed with moderate or severe depressive disorder according to the criteria of the DSM-5; total score of 17-HDRS≥17; never receiving electroconvulsive therapy (ECT)/modified ECT (MECT)/rTMS or other treatments in the past month; having sufficient audio-visual ability and comprehension; signed informed consent statements. Exclusion Criteria: serious or active somatic illness (abnormal index values were more than twice the limit of normal); a history of mania/hypomania; current high risk of suicide (score of item 3 of 17-HDRS ≥ 3); pregnant or lactating women, or planning pregnant women; taking immunosuppressants or vitamins recently.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SSRI group<br>One SSRI is prescribed based on treatment guidelines for major depressive disorder and drug prescription manual. The dose is 20-60mg/day for fluoxetine, 20-40mg/day for paroxetine, 100-300mg/day for fluvoxamine, 50-200mg/day for sertraline, 20-40mg/day for citalopram, 10-20mg/day for escitalopram, respectively. | Drug: SSRIs<br>* One SSRI(No-specified) is prescribed based on treatment guidelines for major depressive disorder and drug prescription manual. The dose is 20-60mg/day for fluoxetine, 20-40mg/day for paroxetine, 100-300mg/day for fluvoxamine, 50-200mg/day for sertraline, 20-40mg/day for citalopram, 10-20mg/day for escitalopram, respectively.<br>|
| Experimental: SSRI plus Sulforaphane group<br>One SSRI is prescribed based on treatment guidelines for major depressive disorder and drug prescription manual. The dose is 20-60mg/day for fluoxetine, 20-40mg/day for paroxetine, 100-300mg/day for fluvoxamine, 50-200mg/day for sertraline, 20-40mg/day for citalopram, 10-20mg/day for escitalopram, respectively. The oral dose of SFN is based on weight. The usage and dosage are as follows: 40-70kg, 4 tablets/day (containing 274μmol of glucosinolates); 70-90kg, 6 tablets/day (containing 411μmol of glucosinolates). Take it once in the morning and evening. | Drug: SSRIs<br>* One SSRI(No-specified) is prescribed based on treatment guidelines for major depressive disorder and drug prescription manual. The dose is 20-60mg/day for fluoxetine, 20-40mg/day for paroxetine, 100-300mg/day for fluvoxamine, 50-200mg/day for sertraline, 20-40mg/day for citalopram, 10-20mg/day for escitalopram, respectively.<br>Dietary Supplement: SSRI plus Sulforaphane<br>* One SSRI(No-specified) is prescribed based on treatment guidelines for major depressive disorder and drug prescription manual. The dose is 20-60mg/day for fluoxetine, 20-40mg/day for paroxetine, 100-300mg/day for fluvoxamine, 50-200mg/day for sertraline, 20-40mg/day for citalopram, 10-20mg/day for escitalopram, respectively. The oral dose of SFN (ZHIYINGUOSU, Shenzhen Fushan Biotech Co. Ltd.) is based on weight. The usage and dosage are as follows: 40-70kg, 4 tablets/day (containing 274μmol of glucosinolates); 70-90kg, 6 tablets/day (containing 411μmol of glucosinolates). Take it once in the morning and evening.<br>|
| No Intervention: Healthy control group<br>No intervention is given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the reduction rate in 17-HDRS total score from baseline to the end of the study | Remission is defined as 17-HDRS total score ≤7; Response is defined as ≥50% decrease from 17-HDRS total score at baseline and 17-HDRS total score>7; Nonresponse is defined as having a reduction of<50% on the total score of 17-HDRS comparing with baseline. at baseline, week 2/4/8/12 after treatment. | at baseline, week 2/4/8/12 after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in levels of serum markers from baseline to the end of the study | changes in levels of serum markers including nuclear factor erythroid-2-related factor 2(Nrf-2), p-Nrf2, Heme Oxygenase-1 (HO-1), malondialdehyde (MDA) and erythrocyte glutathion peroxidase (GPX) from baseline to week 8-12 after treatment | at baseline, week 8-12 after treatment | 
| changes in niacin skin flush response test from baseline to the end of the study | changes in signals of blood flow (typified by maximum blood flow, MBF) detected by the Doppler Laser Flowmetry during the niacin skin flush response test from baseline to week 8-12 after treatment | at baseline, week 8-12 after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Sulforaphane, Niacin skin flush response, Marker, Add-on