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

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.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram; Dietary supplement: Escitalopram+Sulforaphane; Device: Escitalopram+rTMS

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaohua Liu, Dr.; Phone Number: 8613918061085; Email: drliuxiaohua@gmail.com

Study Locations

• China
  • Shanghai, China, 200030
    • Recruiting
    • Shanghai Mental Health Center
    • Contact: Yifeng Shen, Ph.D; Phone Number: 8621-34773657; Email: shenyifeng@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The inclusion criteria are as follows:

1. aged 18-60 years;
2. diagnosed with moderate or severe depressive disorder according to the criteria of the DSM-5;
3. total score of 17-HDRS≥17;
4. never receiving electroconvulsive therapy (ECT)/modified ECT (MECT)/rTMS or other treatments in the past month;
5. 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;
6. having sufficient audio-visual ability and comprehension;
7. signed informed consent statements.

The exclusion criteria are as follows:

1. serious or active somatic illness (abnormal index values were more than twice the limit of normal);
2. a history of mania/hypomania;
3. current high risk of suicide (score of item 3 of 17-HDRS ≥ 3);
4. pregnant or lactating women, or planning pregnant women;
5. taking immunosuppressants or vitamins recently.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / 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.	Drug: Escitalopram; Escitalopram(No-specified) 10-20mg/d, once per day.; 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 .
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.	Drug: Escitalopram; Escitalopram(No-specified) 10-20mg/d, once per 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.

What is the study measuring?

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.

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, malondialdehyde (MDA), superoxide dismutase (SOD) and erythrocyte glutathion peroxidase (GPX)	at baseline, week 8-12 after treatment.

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2019
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): November 30, 2022

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; Sulforaphane; rTMS; Efficacy; Oxidative stress; Marker; Add-on
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antineoplastic Agents; Protective Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Anticarcinogenic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide; Sulforaphane
• Other Study ID Numbers: SHDC12019X09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No