the Safety and Effectiveness of Precise rTMS Based on Neuroimaging in the Treatment of Adolescent Depression With Anhedoniadepression With Anhedonia

A Randomized, Sham-Controlled Trial Evaluating the Safety and Effectiveness of Precise Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy Based on Neuroimaging in Depressed Adolescents With Anhedonia.

This study evaluates a schedule of precise repetitive transcranial magnetic stimulation for depressive adolescent with anhedonia. In this randomized controlled trial, half of the participants will receive repetitive transcranial magnetic stimulation, and the other will receive sham stimulation.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder; Repetitive Transcranial Magnetic Stimulation
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (TMS)

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression among adult. The approved method for treatment is 10Hz stimulation over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been successful for many people with treatment-resistant depression. However, a large percentage of adolescents suffering from major depressive disorder (MDD) do not adequately benefit from currently available treatments. One of the limitations is concerns about the safety and efficacy of antidepressant. Recently, researchers have aggressively pursued better treatment strategy such as rTMS to improve adolescent depression with some preliminary success. This study intends to further explore the safety and efficacy of rTMS in the treatment for adolescent major depressive disorder with anhedonia. This study will also look at the change in neuroimaging biomarkers associated with this treatment.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huaning Wang, doctor; Phone Number: 13609161341; Email: xskzhu@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Wang Huaning; Phone Number: +8613609161341; Email: xskzhu@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, 13 to 18 years of age.
• According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE).
• Meet the threshold on the total HAMD17 score of >/=17 at both screening and baseline visits (Day -7 and Day 0).
• Meet the threshold on the total SHAPS score of >/=20 at both screening and baseline visits (Day -7 and Day 0).
• Not take any antidepressants for two or more weeks before screening.
• In good general health, as ascertained by medical history.
• After fully understanding the treatment of transcranial magnetic stimulation, willing to cooperate with the treatment actively and able to provide informed consent.

Exclusion Criteria:

• Current diagnosis of a Substance Use Disorder, with the exception of nicotine and caffeine dependence.
• Current diagnosis of mental disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is clinically unstable, and/or the focus of the participant's treatment for the past six months or more).
• History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.
• Any other Mental Disorders, Personality Disorders, Intellectual Disability, which at screening is clinically predominant to their MDD.
• Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results.
• Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
• Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
• History of electronic instrument or metal in the head or skull.
• History of epilepsy.
• History of cardiovascular disease or cardiac event.
• History of OCD.
• History of autism spectrum disorder.
• History of rTMS exposure.
• Other situations judged by the researchers to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rTMS Active; Blinded Active TMS coil. Active repetitive Transcranial Magnetic Stimulation (rTMS) and Sertraline (dosage form: pill, dosage: 50mg, frequency and duration: At the beginning of the treatment, the dose of 25mg/ was taken for 1-3 days and adjusted to 50mg/ days for 4-7 days. If there were no dose-limiting adverse events, the dose could be titrated to 100mg/ days in the second week. The dose could be flexibly adjusted within the range of 100~150mg/ days until a satisfactory clinical response was achieved. After that, the drug dose was kept unchanged as far as possible. Take it once a day, after a meal at a relatively fixed time in the morning.)	Device: Transcranial Magnetic Stimulation (TMS); Compare active coil with sham coil.; Other Names: Sertraline; TMS
Sham Comparator: rTMS Sham; Blinded Sham TMS coil. Sham Transcranial Magnetic Stimulation (TMS) and Sertraline (dosage form: pill, dosage: 50mg, frequency and duration: At the beginning of the treatment, the dose of 25mg/ was taken for 1-3 days and adjusted to 50mg/ days for 4-7 days. If there were no dose-limiting adverse events, the dose could be titrated to 100mg/ days in the second week. The dose could be flexibly adjusted within the range of 100~150mg/ days until a satisfactory clinical response was achieved. After that, the drug dose was kept unchanged as far as possible. Take it once a day, after a meal at a relatively fixed time in the morning.)	Device: Transcranial Magnetic Stimulation (TMS); Compare active coil with sham coil.; Other Names: Sertraline; TMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in the Snaith-Hamilton Pleasure Scale (SHAPS)Score From Pre-treatment to 8-weeks	A 14 item self-assessment questionnaire used to measure the severity of anhedonia symptom in patients with mood disorders. Scale range - 14 to 56 with higher score indicative of greater anhedonia symptomology.	Pre-treatment and 8-weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in the Hamilton Rating Scale for Depression (HAM-17)	A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were prespecified; only those time points for which data were collected are reported.	Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)	A diagnostic questionnaire used to measure the severity of depressive symptoms. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.	Time Frame: Pre-treatment to 1 week and15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Chinese version of Temporal Experience of Pleasure Scale(CV-TEPS)	A 20 item self-assessment questionnaire, eleven items used to measure anticipatory anhedonia, and nine items used to evaluate consummatory anhedonia. Scale range - 0 to 140 with lower score indicative of greater anhedonia symptomology.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Chinese version of Beck Scale for Suicide Ideation（BSI-CV）	A 19 item questionnaire used to evaluate the severity of suicidal ideation. The scale includes two subscales of suicidal ideation (Current suicidal ideation, BSI-C) and suicidal ideation (Suicidal ideation at one's worst point, BSI-W) in the last week. Scale range - 0 to 38, the higher the score of the subscale, the higher the level of suicidal ideation in the last week or the most serious.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Insomnia Severity Index Scale （ISI）	The questionnaire consists of seven items: the severity of insomnia symptoms, the satisfaction of sleep patterns, the effects of insomnia on daytime function, the effects of insomnia on subjects' quality of life, and the degree of worry or depression caused by insomnia. Scale range - 0 to 28 with higher score indicative of greater Insomnia symptomology.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Clinical Global Impression (CGI)	The questionnaire used to evaluate the clinical efficacy, it includes three parts: severity of illness (SI), global improvement (GI) and effect index (EI). With higher score indicative of more serious disease and worse effect.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Percent Change in the Snaith-Hamilton Pleasure Scale (SHAPS)	A 14 item self-assessment questionnaire used to measure the severity of anhedonia symptom in patients with mood disorders. Scale range - 14 to 56 with higher score indicative of greater anhedonia symptomology.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment
Change From Baseline Functional Connectivity to 15-days Post-treatment	We will assess change in resting state fMRI functional connectivity of the nucleus accumbens to the Dorsolateral Prefrontal Cortex and within the reward-related circuits	Time Frame: Pre-treatment, immediately post-treatment (on day 15)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
A digital tool named THINC-it® to help assess cognitive functioning	THINC-it® is a screening tool designed to measure cognition, is based on a combination of specific (traditional) neuropsychological tests assessing cognitive functioning, in conjunction with a patient-reported questionnaire.	Time Frame: Pre-treatment to 1 week and 15days, 4 weeks, 6 weeks and 8 weeks post-treatment

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Depressive Disorder; Anhedonia; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Sertraline
• Other Study ID Numbers: KY20222165-F-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No