A Comparative Study on Efficacy and Safety of add-on Sulforaphane or rTMS to Escitalopram for Major Depressive Disorder With Poor Response to Initial Treatment

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05145270

Collaborator

(none)

180

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A 12-week, randomized controlled trial (RCT) with parallel grouping design will be conducted to compare the efficacy and safety of different treatments. One hundred and eighty adults diagnosed with major depressive disorder (MDD) with no or poor response to initial antidepressant treatment will be recruited. Then all the patients will be 1:2:2 randomly assigned to different intervention groups including escitalopram, escitalopram plus sulforaphane (SFN) , and escitalopram plus repetitive transcranial magnetic stimulation (rTMS). Clinical symptoms and side-effects will be evaluated or recorded using the 17-Hamilton Depression Rating Scale (17-HDRS), the Hamilton Anxiety Scale (HAMA), side-effects sheet, etc., at Critical Decision Points (CDP) including weeks 2, 4, 8 and 12 after treatment. Blood cell counting, biochemical, and electrocardiogram examination will be performed at weeks 4, 8 and 12 after treatment in order to evaluate the effect of different interventions on the physical condition. In addition, niacin skin flush response and serum markers including nuclear factor erythroid-2-related factor 2(Nrf-2), p-Nrf2, malondialdehyde (MDA), superoxide dismutase (SOD) and erythrocyte glutathion peroxidase (GPX) will be tested 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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Dietary Supplement: Escitalopram+Sulforaphane Device: Escitalopram+rTMS Drug: Escitalopram	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All the participants will be 1:2:2 randomly assigned to different intervention groups including escitalopram, escitalopram plus sulforaphane (SFN) , and escitalopram plus repetitive transcranial magnetic stimulation (rTMS).All the participants will be 1:2:2 randomly assigned to different intervention groups including escitalopram, escitalopram plus sulforaphane (SFN) , and escitalopram plus repetitive transcranial magnetic stimulation (rTMS).

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Comparative Study on Efficacy and Safety of add-on Sulforaphane or rTMS to Escitalopram for Major Depressive Disorder With Poor Response to Initial Treatment

Actual Study Start Date :

Nov 30, 2019

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Escitalopram The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day.	Drug: Escitalopram Escitalopram(No-specified) 10-20mg/d, once per day.
Experimental: Escitalopram plus Sulforaphane The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day. 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.	Dietary Supplement: Escitalopram+Sulforaphane Escitalopram(No-specified) 10-20mg/d, once per day; Sulforaphane(ZHIYINGUOSU, Shenzhen Fushan Biotech Co. Ltd.). 40-70kg, 4 tablets/day (containing 274μmol of glucosinolates); 70-90kg, 6 tablets/day . Drug: Escitalopram Escitalopram(No-specified) 10-20mg/d, once per day.
Experimental: Escitalopram plus rTMS The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day. rTMS is delivered to the left dorsolateral prefrontal lobe position. Stimulation parameters are set to be 80 stimulation strings of 10Hz with an interval of 12 seconds. Each stimulation string includes 30 stimulations lasting for 3 seconds. One session includes 2400 stimulation strings lasting for 19 minutes and 40 seconds. The course of rTMS treatment includes 20 sessions, once a day or twice a day.	Device: Escitalopram+rTMS Escitalopram(No-specified) 10-20mg/d, once per day; rTMS: rTMS is delivered to the left dorsolateral prefrontal lobe position. Stimulation parameters are set to be 80 stimulation strings of 10Hz with an interval of 12 seconds. Each stimulation string includes 30 stimulations lasting for 3 seconds. One session includes 2400 stimulation strings lasting for 19 minutes and 40 seconds. The course of rTMS treatment includes 20 sessions, once a day or twice a day. Drug: Escitalopram Escitalopram(No-specified) 10-20mg/d, once per day.

Arm

Intervention/Treatment

Active Comparator: Escitalopram

The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day.

Drug: Escitalopram

Escitalopram(No-specified) 10-20mg/d, once per day.

Experimental: Escitalopram plus Sulforaphane

The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day. 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.

Dietary Supplement: Escitalopram+Sulforaphane

Escitalopram(No-specified) 10-20mg/d, once per day; Sulforaphane(ZHIYINGUOSU, Shenzhen Fushan Biotech Co. Ltd.). 40-70kg, 4 tablets/day (containing 274μmol of glucosinolates); 70-90kg, 6 tablets/day .

Drug: Escitalopram

Escitalopram(No-specified) 10-20mg/d, once per day.

Experimental: Escitalopram plus rTMS

The dose of Escitalopram based on treatment guidelines for major depressive disorder and drug prescription manual is 10-20mg/day, once per day. rTMS is delivered to the left dorsolateral prefrontal lobe position. Stimulation parameters are set to be 80 stimulation strings of 10Hz with an interval of 12 seconds. Each stimulation string includes 30 stimulations lasting for 3 seconds. One session includes 2400 stimulation strings lasting for 19 minutes and 40 seconds. The course of rTMS treatment includes 20 sessions, once a day or twice a day.

Device: Escitalopram+rTMS

Escitalopram(No-specified) 10-20mg/d, once per day; rTMS: rTMS is delivered to the left dorsolateral prefrontal lobe position. Stimulation parameters are set to be 80 stimulation strings of 10Hz with an interval of 12 seconds. Each stimulation string includes 30 stimulations lasting for 3 seconds. One session includes 2400 stimulation strings lasting for 19 minutes and 40 seconds. The course of rTMS treatment includes 20 sessions, once a day or twice a day.

Drug: Escitalopram

Escitalopram(No-specified) 10-20mg/d, once per day.

Outcome Measures

Primary Outcome Measures

the reduction rate in 17-HDRS total score from baseline to the end of the study [at baseline, week 2/4/8/12 after treatment.]
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.

Secondary Outcome Measures

changes in levels of serum markers from baseline to the end of the study [at baseline, week 8-12 after treatment.]
changes in levels of serum markers including nuclear factor erythroid-2-related factor 2(Nrf-2), p-Nrf2, malondialdehyde (MDA), superoxide dismutase (SOD) and erythrocyte glutathion peroxidase (GPX)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

The inclusion criteria are as follows:

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;
no response or poor response (having a reduction of <20% on the total score of the 17-item Hamilton Depression Scale compared with the baseline) to adequate antidepressants (except escitalopram) treatment for at least 4 weeks;
having sufficient audio-visual ability and comprehension;
signed informed consent statements.

The exclusion criteria are as follows:

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.