Dorsomedial Prefrontal Neuromodulation in Treatment-resistant Depression

NCT05422417 | Unknown

• 1 other identifier: IRB-TPEVGH No.: 2021-08-006A#1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is a common and troublesome disorder, with high risk of physical and psychiatric comorbidity. At least one-third of patients could not achieve a response after several antidepressant trials, so-called treatment-refractory depression (TRD). The high-frequency repetitive transcranial magnetic stimulation (rTMS) or intermittent theta-burst stimulation (iTBS) at left-sided dorsolateral prefrontal cortex (DLPFC) have a response rate of 40-60%. Obviously, not all TRD patients achieve the remitted state after treatment with antidepressants or DLPFC-rTMS, which may result from the heterogeneity of MDD. More and more evidence, such as brain lesion studies, deep brain stimulation, open-labeled rTMS case series, and neuroimaging studies, suggests that dorsomedial prefrontal cortex (DMPFC) might play a more central role in the pathophysiology of major depression. The DMPFC demonstrated as a "dorsal nexus" phenomenon in depression, which means a unique brain region where cortical networks for affect regulation, default mode control and cognitive control coverage in depressed subjects but not in healthy persons. In addition, another meta-analysis of resting-state functional MRI (fMRI) demonstrated the abnormal functional connectivity from DMPFC. These abnormalities of networks were highly associated with several depressive symptoms such as anhedonia, emotional regulation, somatic markers, rumination, self-reflection, poor attention and poor decision-making. However, only a handful of studies investigated the brain stimulation targeting DMPFC and the further changes in brain functional connectivity. The clinical efficacy and the fMRI changes of prolonged intermittent theta-burst stimulation (piTBS) and 20Hz- rTMS targeting bilateral DMPFC were investigated, and the predictive value of baseline networks by fMRI for antidepressant responses was also assessed to find a reliable approach to gauge treatment response prospectively.

Conditions

Treatment-resistant Depression; Major Depressive Disorder

Keywords

rTMS; prolonged iTBS; brain stimulation; intermittent theta burst stimulation

Outcome Measures

Primary Outcomes (2)

• Change in 17-item Hamilton Depression Rating Scale

  the altered 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)

  Time Frame: Baseline, Week 1, Week 2, Week 3 (one week after brain stimulation), Week 6, Week 14(three-month after brain stimulation)

• Change in anxiosomatic cluster symptoms derived 17-item Hamilton Depression Rating Scale

  the altered anxiosomatic cluster symptoms (range, 0 to 26, with higher scores indicating more severe anxiosomatic symptoms).The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis.

  Time Frame: Baseline, Week 1, Week 2, Week 3 (one week after brain stimulation), Week 6, Week 14(three-month after brain stimulation)

Secondary Outcomes (22)

• Response rate after 2-week treatment at the end of the trial, one month and three months after.

  Time Frame: Week 2, Week 6(one month after brain stimulation), Week 14(three-month after brain stimulation)

• Remission rate after 2-week treatment at the end of the trial, one month and three months after.

  Time Frame: Week 2, Week 6(one month after brain stimulation), Week 14(three-month after brain stimulation)

• Changes in Clinical Global Index

  Time Frame: Baseline, Week 1, Week 2, Week 3 (one week after brain stimulation), Week 6, Week 14(three-month after brain stimulation)

• Changes in depression severity, rated by self-reported

  Time Frame: Baseline, Week 1, Week 2, Week 3 (one week after brain stimulation), Week 6, Week 14(three-month after brain stimulation)

• Changes in Young Mania Rating Scale

  Time Frame: Baseline, Week 1, Week 2, Week 3 (one week after brain stimulation), Week 6, Week 14(three-month after brain stimulation)

Study Arms (3)

Prolonged intermittent theta-burst(iTBS)-DMPFC

EXPERIMENTAL

This active group will receive prolonged intermittent theta-burst(iTBS) on the dorsomedial prefrontal cortex(DMPFC)

Device: Prolonged intermittent theta burst stimulation (piTBS)

20Hz rTMS-DMPFC

EXPERIMENTAL

This active group will receive 20Hz rTMS on the DMPFC

Device: 20Hz rTMS

Sham prolonged iTBS-DMPFC or 20Hz rTMS-DMPFC

SHAM COMPARATOR

Patients in the sham group will receive the same prolonged iTBS or 20Hz rTMS performed by a sham coil.

Device: sham control

Interventions

Prolonged intermittent theta burst stimulation (piTBS) DEVICE

Participants in the prolonged dosage (1800 pulse) of intermittent TBS (iTBS) active stimulation group will receive 2-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to the bilateral DMPFC, twice a day. Stimulation will be delivered to the DMPFC using a stimulator.

Prolonged intermittent theta-burst(iTBS)-DMPFC

20Hz rTMS DEVICE

Participants in the 20 Hz rTMS (2000 pulse) active stimulation group will receive 2-week 2s- and-10s off, total 50 cycles at each hemisphere/session, at an intensity of 100% resting motor threshold (MT) to the bilateral DMPFC, twice a day. Stimulation will be delivered to the DMPFC using a stimulator.

20Hz rTMS-DMPFC

sham control DEVICE

Half of the patients in the sham group received 2-week the same prolonged iTBS parameter stimulation (sham- prolonged iTBS), and the other half received the same 20 Hz rTMS parameter stimulation using a sham coil (sham-20 Hz rTMS), which also improved the blinding process

Sham prolonged iTBS-DMPFC or 20Hz rTMS-DMPFC

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with a recurrent major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Diagnoses were established after taking a thorough medical history and conducting a semistructured interview by administering the Mini International Neuropsychiatric Interview (MINI);
• Recruited participants had to have a Clinical Global Impression - Severity score of at least four and a total score of at least 18 on the 17-items Hamilton Depression Rating Scale (HDRS-17);
• Patients were qualified if they failed to respond to at least one adequate antidepressant treatment in their current episode (for example, failed to achieve 50% improvement of depression to an equivalent daily dose of 10 to 20 mg of escitalopram for at least eight weeks);
• Stabilized treatment: keeping current antidepressant drug treatment, including the dose at least for four weeks before this trial and during the trial period; keep the stabilized psychotherapy at least for three months and no anticipated adjustment of types of psychotherapy and the frequency.

You may not qualify if:

• Patients with Bipolar I and II disorder, schizophrenia, organic brain syndromes, or other major physical illnesses;
• Patients who had received or will receive brain surgery or receive brain metal implantation (for example, neurostimulator) or received cardiac pacemakers;
• Patients who had strong suicidal ideation within one week ( 3 points for third item of HDRS-suicidality)
• Patients who had abnormal finding in the brain ( for example, brain tumor or arteriovenous malformation) or neurological disease ( for example, history of meningitis, encephalitis, epilepsy, stroke or neurodegenerative disease)
• Pregnancy;
• Patients who have metal implantation in the body, including cochlear implant, prosthetic heart valve, neurostimulator, clips.. etc
• Patients who also failed to respond after receiving one completed course of electroconvulsive therapy (ECT) treatment or left dorsolateral prefrontal brain stimulation (adequate dose and adequate duration of ECT or DLPFC-rTMS and had followed up to monitor the efficacy at least for three months)
• Claustrophobia for MRI screening;
• Those who cannot follow the protocols, and did not sign informed consent proved by the institutional review board (IRB)

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (1)

Taipei Veterans General Hospital, Taiwan

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Chih-Ming Cheng, M.D.

  Taipei Veterans General Hospital, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chih-Ming Cheng, M.D.

CONTACT

+886 2 28757027; vdodaco@gmail.com

Chih-Ming Cheng, M.D.

CONTACT

886 2 28757027

Study Design

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

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 16, 2022
• Study Start: June 7, 2022
• Primary Completion: September 30, 2025
• Study Completion: December 31, 2025
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

TW (1)