Using Repetitive Transcranial Magnetic Stimulation to Study the Role of Frontostriatal Circuit in Major Depressive Disorder

NCT05212636 | Completed

• 1 other identifier: B-BR-108-092
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is a common, severe, and often life-threatening illness that involves the body, mood, and thoughts. The natural course of MDD tends to worsen without treatment, while people with MDD can lead healthy and productive lives when the illness is effectively treated. Up to 50% of the patients show no response to current available antidepressants.Two major non-invasive brain stimulation (NIBS) tools have been applied for the treatment of psychiatric diseases so far, transcranial magnetic and direct current stimulation (TMS, tDCS). TMS induces a strong magnetic field (magnetic pulses) through the skull into the brain, which generates electrical currents in brain tissue and induces neuronal firing, leading to after-effects, i.e. neuroplasticity, eventually. Neuronal effects of rTMS has been proven to last beyond the actual time of stimulation, enabling altered brain activity for an extended period of time. Adding on rTMS treatment could even give a chance to treat the physical comorbidities and enhance cognitive function in MDD. Nevertheless, underlying neurobiological mechanism of rTMS treatment remains unclear. Reports showed chronic psychosocial stressors are associated with altered frontal-striatal circuitry activation and connectivity. Indeed, aberrant fronto-striatal connectivity and reduced sustain fronto-striatal activation were noticed in MDD patients. However, the specific correlations between fronto-striatal connectivity changes and rTMS treatment outcomes in MDD remain unclear. In this study fMRI will be used to measure the possible correlations between the fronto-striatal circuit activation / connectivity with (1) mood symptoms presentations, (2) neurocognitive measurements, (3) HPA and ANS activities, and (4) immune and metabolic status (cytokines, adipokines and insulin levels) in patients with MDD. Then the possible changes in fronto-striatal FC over a four-week treatment course with 10 Hz rTMS stimulation to left dorsolateral prefrontal cortex will be measured. The FC changes will be tested to find out whether correlate with treatment outcomes, HPA and ANS activity; and immune/metabolic indices changes. We hypothesize that rTMS as an add-on therapy would change the fronto-striatal FC that correlated with mood symptom improvement, neurocognitive measurements, HPA and ANS activity, inflammatory and metabolic homeostasis in patients with MDD.

Conditions

Depressive Disorder, Major

Keywords

Repetitive Transcranial Magnetic Stimulation (rTMS); Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (8)

• Change from Baseline Mood Symptom Severity at Numerous Timepoints within 3 Months Period

  Evaluation for disease severity by using the 17-item Hamilton Rating Scale for Depression (HAM-D) by trained senior psychiatrists. The same rater administers the scale for each patient. Higher scores represent worse mood symptoms.

  Week 0, Week 1, Week 2, Week 3, Week 4, Week 8, Week 12.

• Iowa gambling task (IGT) with Functional MR Imaging

  The subject will be asked to turn a card from 4-decks voluntarily, and maximize gains and minimize losses during the game.

  Week 0

• Change from Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR) index at Numerous Timepoints within 3 Months

  The homeostasis model assessment-estimated insulin resistance (HOMA-IR) index is calculated as the product of the fasting plasma insulin level (uIn/ml) and the fasting plasma glucose level (mg/dl), divided by 405. Insulin resistance is defined as HOMA-IR ≥2.5.

  Week 0, Week 4, Week 8, Week 12

• Change from Baseline Waist and Hip Circumference at Numerous Timepoints within 3 Months

  Waist and hip circumference (to the nearest 0.1 cm)

  Week 0, Week 4, Week 8, Week 12

• Change from Baseline Fasting Serum Leptin Level at Numerous Timepoints within 3 Months

  Measured using ELISA method (Linco Research, USA)

  Week 0, Week 4, Week 8, Week 12

• Change from Baseline Fasting Serum Lipid Level at Numerous Timepoints within 3 Months

  Fasting total cholesterol, high density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglyceride (TG) concentrations will be measured.

  Week 0, Week 4, Week 8, Week 12

• Change from Baseline Immunological Markers at Numerous Timepoints within 3 Months

  The fasting plasma CRP level will be assessed using an high-sensitivity CRP ELISA kit (Bender MedSystems, USA).

  Week 0, Week 2, Week 3, Week 4, Week 8, Week 12

• Change from Baseline Neurocognitive performance at 3 Months

  Neurocognitive performance will be assessed using Continuous Performance Test (CPT), Finger-Tapping Test (FTT) and Wisconsin Card-Sorting Test (WCST).

  Week 0, Week 12

Study Arms (1)

MDD patient with HRSD score of at least 18

EXPERIMENTAL

MDD patients who meet the DSM-5 diagnostic criteria of MDD and their current episode show a 17-Item Hamilton Rating Scale for Depression (HRSD) score of at least 18

Device: Repetitive transcranial magnetic stimulation (rTMS)

Interventions

Repetitive transcranial magnetic stimulation (rTMS) DEVICE

A total of 12 sessions of rTMS (5 sessions per week for 2 weeks, follow by 1 session per week for next 2 weeks) .

Also known as: Antidepressants

MDD patient with HRSD score of at least 18

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• meet the DSM-5 diagnostic criteria and their current episode show a 17-item Hamilton Rating Scale for Depression (HRSD-17) score of at least 18
• show no clinical response to an adequate dose of an antidepressant
• could not tolerate at least two antidepressants in the current episode will be enrolled consecutively by trained psychiatrists
• Patients should receive a stable antidepressant regimen for at least 4 weeks before screening and continue during treatment

You may not qualify if:

• had DSM-5 diagnosis for substance abuse within the past three months
• had taken monoamine oxidase inhibitors
• had an organic mental disorder, mental retardation, dementia, or other diagnosed neurological illness
• had a surgical condition or a major physical illness
• underwent course of electroconvulsive therapy (ECT) within the last three months
• the presence of a cardiac pacemaker, intracranial implant, or metal in the cranium
• taking any anticonvulsant or if more than three adequate antidepressant trials had failed (determined by antidepressant treatment history form).

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead
• Ministry of Science and Technology, Taiwan: collaborator

Study Sites (1)

National Cheng-Kung University

Tainan, 704, Taiwan

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor, Visiting Staff Psychiatrist of Department of Psychiatry, Professor (joint appointment) of Institute of Behavioral Medicine

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: January 28, 2022
• Study Start: August 1, 2020
• Primary Completion: October 28, 2021
• Study Completion: October 31, 2021
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

TW (1)