Intermittent Theta-burst Stimulation for Major Depression: an Intensity-response Study

NCT06392867 | Recruiting

• 1 other identifier: HSEARS20221101008
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

Brief Summary

The United States Food and Drug Administration (FDA) approved intermittent theta-burst stimulation (iTBS) in 2018 as a form of repetitive transcranial magnetic stimulation (rTMS). Hospitals worldwide use it to treat major depressive disorder (MDD). It is safe, effective, even for depressed patients unable to respond to standard pharmacological treatment and is more efficient than standard rTMS. In accordance with the approved treatment protocol, patients experience considerable sensory discomfort at a stimulation intensity of 120% of their resting motor threshold (rMT). Antidepressant effects of iTBS are believed to be mediated by modulating prefrontal excitability. There is still a lack of evidence to support the choice of 120% rMT as the optimal stimulation intensity, and the presumed superiority of higher stimulation intensities over lower intensities has yet to be proven. This knowledge gap has clinical implications since more tolerated treatments may lead to greater adherence, resulting in improved outcomes. The current study proposes a randomized, triple-arm, controlled trial to compare the efficacy of iTBS at 75% (iTBS75) and 120% (iTBS120) rMT with sham iTBS (SiTBS). Based on the following considerations, SiTBS was selected to be compared with iTBS75 and iTBS120: SiTBS will reveal placebo antidepressant effects and serve as a control. iTBS75 is selected because iTBS at 80% aMT exhibits significant excitatory effects on the motor cortex and corresponds to approximately 70% rMT. There is however, a distance of about 12.7mm between the coil and the motor cortex, whereas 14.4mm separates the coil from the dorsolateral prefrontal cortex (DLPFC). Accordingly, a resting motor threshold of 70% at the motor cortex corresponds to a distance-adjusted rMT of 75% at the DLPFC. Lastly, iTBS120 is chosen as the standard stimulation intensity in current iTBS depression trials. It is our intention to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers. Thus, our study can contribute to establishing a treatment regimen with increased adherence and lower withdrawal rates.

Conditions

Depression, Unipolar

Keywords

Transcranial magnetic stimulation, TMS; Major Depressive Disorder; iTBS; TMS treatment for depression

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg depression rating scale (MADRS)

  The Montgomery-Åsberg Depression Rating Scale is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Response rate after treatment (Montgomery-Asberg depression rating scale, MADRS reduction ≥50% of baseline) 0 to 6: normal /symptom absent. 7 to 19: mild depression. 20 to 34: moderate depression. 35 to 60: severe depression.

  through study completion, an average of 1 month

Secondary Outcomes (3)

• Patient Health Questionnaire-9 (PHQ-9)

  through study completion, an average of 1 month

• Subjective Happiness Scale (SHS)

  through study completion, an average of 1 month

• Verbal Analogue Scale (VAS) Pain level

  through study completion, an average of 1 month

Study Arms (3)

SiTBS

SHAM COMPARATOR

The participants will not receive any benefit from the intermittent theta-burst stimulation (iTBS) if they use the inactive side of the coil.

Device: intermittent theta-burst stimulation (iTBS)

iTBS75

ACTIVE COMPARATOR

The intensity of intermittent theta-burst stimulation (iTBS) applied to the participant will be 75% of their individual rest motor threshold (rMT).

Device: intermittent theta-burst stimulation (iTBS)

iTBS120

ACTIVE COMPARATOR

The intensity of intermittent theta-burst stimulation (iTBS) applied to the participant will be 120% of their individual rest motor threshold (rMT).

Device: intermittent theta-burst stimulation (iTBS)

Interventions

intermittent theta-burst stimulation (iTBS) DEVICE

iTBS treatment will be performed as comprising 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz). iTBS consists of 2-second trains with an inter-train-interval of 8 seconds. Repeat trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20) which equals the standard number of pulses in a daily iTBS treatment session, as approved by the FDA. The stimulation site over the left DLPFC will be determined using the international 10-20 system for EEG electrodes corresponding to the F3 location. 20 daily treatment sessions will be performed from Mondays to Fridays for four weeks for all included patients. Treatments will be performed at the brain stimulation laboratory at the Hong Kong Polytechnic University. Stimulation will be delivered using a MagPro X100 model (details about MagPro X100: magventure.com/en\_eur/products/magpro-x100/ ) and a Cool-B65 A/P Butterfly Coil is used in this study.

SiTBS; iTBS120; iTBS75

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are aged between 18 and 70;
• have a MDD diagnosis, single or recurrent episode, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria and confirmed by means of the Mini-International Neuropsychiatric Interview (MINI);
• have a score of at least 18 on the 17-item Hamilton Rating Scale for Depression (HDRS17) in their current episode;
• have failed to have a clinically significant response to two or more standard antidepressant treatments during their current episode;
• have received stable psychopharmacological treatment within 4 weeks prior to screening; and
• have normal thyroid function, Complete Blood Count, electrolytes, and liver enzyme levels based on pre-study blood work.

You may not qualify if:

• have a history of substance abuse or dependence in the past 3 months;
• have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump;
• show active suicidal intent (MADRS item 10 score \>4);
• are pregnant;
• have a lifetime MINI diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms;
• take antiepileptic drugs or benzodiazepines corresponding to a dose of \>1 mg lorazepam per day;
• have had initiation or dose change of any psychotropic medication in the 4 weeks prior to screening or
• have undergone TMS in the past.

Sponsors & Collaborators

• The Hong Kong Polytechnic University: lead
• Health and Medical Research Fund: collaborator

Study Sites (1)

The Hong Kong Polytechnic University

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Georg Kranz, PhD

  The Hong Kong Polytechnic University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georg Kranz, PhD

CONTACT

27664838; georg.kranz@polyu.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Prior to the treatment, each participant will visit The Hong Kong Polytechnic University on a separate day. During the first visit, the researcher will also measure each participant's rMT. The PI will randomly assign the participant to different groups, such as sham group, 75% group, and 120% group, and calculate the maximum intensity of treatment based on the respective groups of the participant. To provide individualized treatment intensity to each participant, the TMS operator will receive the information from the PI and perform the treatment according to the determined intensity. The operator does not know the participant's rMT and sham coil is used. Furthermore, the participants have never received TMS treatment before taking part in this study, so they do not understand the difference between a placebo and a real treatment.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Patients with Major Depressive Disorder will undergo daily intermittent theta-burst stimulation (iTBS) at left DLPFC, 20 sessions in 4 weeks. It is to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers. The current study proposes a randomized, triple-arm, controlled trial to compare the efficacy of iTBS at 75% (iTBS75) and 120% (iTBS120) rMT with sham iTBS (SiTBS). Based on the following considerations, SiTBS was selected to be compared with iTBS75 and iTBS120: SiTBS will reveal placebo antidepressant effects and serve as a control.

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: May 1, 2024
• Study Start: January 8, 2024
• Primary Completion: April 26, 2026
• Study Completion (Estimated): October 26, 2026
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)