Intensive Accelerated iTBS for the Treatment-Resistant Depression

NCT06166082 | Completed DMC

• 1 other identifier: CPL TRD_aiTBS_Multicenter
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a multicenter, randomized, double-blind, and sham-controlled trial using most intensive aiTBS protocol (10 sessions daily over 5 consecutive days at triple the standard per-session dose) to investigate the antidepressant efficacy for treatment-resistant depression (TRD). Patients will be recruited and randomly assigned (1:1 ratio) to receive active or sham groups from 5 hospitals in China. The interventions will last for 5 days and both groups will be followed up for 8 weeks on the same time schedules. During the intervention and at least the first 4 weeks of post-treatment, participants will keep a stable antidepressant regimen. The individualized target in the left dorsolateral prefrontal cortex (DLPFC) will be generated from 30 minutes of resting-state functional MRI collected at baseline.

Conditions

Treatment Resistant Depression

Keywords

Treatment Resistant Depression; TRD

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS has an overall score range from 0-60, with higher scores corresponding to higher levels of depression.

  Pretreatment (baseline), 28 days post-treatment

Secondary Outcomes (9)

• Change in MADRS

  Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 56 days Post-treatment]

• Change in the Hamilton Rating Scale for Depression (HAMD-17)

  Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]

• Change in the Hamilton Rating Scale for Depression (HAMD-6) Score

  Baseline, Day 1, 2, 3, 4 in treatment, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]

• Change in Quick Inventory of Depressive Symptomatology Self-Report (QIDS_SR)

  Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]

• Safety estimated using YMRS

  Baseline, Day 5 (Immediate Post-treatment)

Study Arms (2)

Active iTBS-DLPFC

EXPERIMENTAL

The active group will receive active iTBS. Treat 10 times a day with 1800 pulses per day for consecutive 5 days, with 50 minutes inter-session intervals.

Device: Active iTBS-DLPFC

Sham iTBS-DLPFC

SHAM COMPARATOR

The sham group will receive sham iTBS. Treat 10 times a day with 1800 pulses per day for consecutive 5 days, with 50 minutes inter-session intervals.

Device: Sham iTBS-DLPFC

Interventions

Active iTBS-DLPFC DEVICE

Participants will receive 10 sessions per day of 1800 pulses per session, lasting for 5 days.

Active iTBS-DLPFC

Sham iTBS-DLPFC DEVICE

The parameters in the sham arms are the same as the active stimulation groups. Stimulation was delivered by the same device as the active group fitted with a sham coil.

Sham iTBS-DLPFC

Eligibility Criteria

• Age: 22 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for depression disorder without psychotic symptoms, and currently experiencing a recurrence episode;
• Hamilton Depression Scale (HAMD-17) scores for 17 items ≥ 20 points, and the Montgomery Asberg Depression Rating Scale (MADRS) score is ≥ 20 points;
• hospitalized/outpatient patients aged ≥ 22 and ≤ 65 years old, male or female;
• The Maudsley Staging Method (MSM) assesses patients as at least moderate refractory (MSM score ≥ 7 points);
• Stable use of antidepressants for 4 weeks before randomization, with the type of antidepressant used being selective serotonin reuptake Selective serotonin reuptake inhibitors (SSRIs) or/and serotonin and norepinephrine reuptake Serotonin-norepinephrine reuptake inhibitors (SNRIs), the therapeutic dose is within the dosage range as the drug manual recommended;
• Understand the trial and sign the informed consent form.

You may not qualify if:

• Meets DSM-5 diagnostic criteria for other mental disorders, including schizophrenia spectrum disorders, bipolar and related disorders, and psychiatric disorders Developmental disorders, neurocognitive disorders, or depression caused by substances and/or drugs, or other medical problems;
• Individuals with pacemakers, cochlear implants, or other metal objects, as well as any electronic devices implanted in the body, and those with claustrophobia Contraindications for magnetic resonance imaging scans such as fear, and contraindications for rTMS treatment;
• History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold Syndromes, or seizures within the past 12 months;
• Received TMS treatment before participating in the trial;
• Individuals who have received ECT or phototherapy within three months;
• No response to ECT treatment (\>8 times);
• Previously received antidepressant treatment with implanted devices (such as DBS, VNS);
• Concomitant organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumors, etc.) and a history of severe brain injury;
• Complicated with serious heart, liver, kidney diseases, diabetes, and other serious physical diseases, which cause abnormal symptoms and signs of brain nerves, Or physical exhaustion;
• Women of childbearing age who are currently pregnant, breastfeeding, or planning or may become pregnant during the trial period;
• Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past year;
• First-degree relatives suffer from bipolar disorder;
• High risk of suicide;
• Difficulty in communication to understand or follow instructions, and unable to cooperate with treatment and evaluation;
• Current in clinical trials of other drugs or physical therapies (DBS, ECT, rTMS);

Sponsors & Collaborators

• Changping Laboratory: lead
• Xianyue Hospital, Xiamen: collaborator
• Hebei Mental Health Center, Baoding: collaborator
• HuiLongGuan Hospital, Beijing: collaborator
• Zhumadian Second People's Hospital, Zhumadian: collaborator
• Wuhan Mental Health Centre: collaborator

Study Sites (5)

Hebei Mental Health Center

Baoding, China

Location

HuiLongGuan Hospital

Beijing, China

Location

Wuhan Mental Health Center

Wuhan, China

Location

Xianyue Hospital

Xiamen, China

Location

Zhumadian Second People's Hospital

Zhumadian, China

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Hesheng Liu, Ph.D.

  Changping Laboratory

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2023
• First Posted: December 12, 2023
• Study Start: December 22, 2023
• Primary Completion: March 21, 2025
• Study Completion: April 21, 2025
• Last Updated: May 11, 2026

Record last verified: 2026-05

Locations

CN (5)