The Cerebral and Cognitive Changes After Intermittent Theta Burst Stimulation (iTBS) Treatment for Depression

The Cerebral and Cognitive Changes After Intermittent Theta Burst Stimulation (iTBS) Treatment for Depression A Randomised Double-blind Sham-controlled Trial

The present project aims to assess the neurocognitive impact of a two-week once-a-day regimen of intermittent theta burst stimulation (iTBS) compared to sham iTBS, when targeting the left dorsolateral prefrontal cortex (LDLPFC) in clinically depressed outpatients. The study investigates the relationships between changes in cerebral measures and cognitive performance on an N-back task in relation to the antidepressive effect following iTBS.

Study Overview

• Status: Recruiting
• Conditions: Depression, Unipolar; Depression Moderate
• Intervention / Treatment: Device: Intermittent Theta Burst Stimulation

Detailed Description

The study is a randomized sham controlled double blind clinical trial in which the changes in cortical functions associated with the anti-depressive effect of two weeks of once-a-day neuronavigated iTBS over the left dorsolateral prefrontal cortex (LDLPFC) will be investigated in comparison to sham iTBS. Participants will be recruited prospectively, and the study is performed at a single university hospital. After written informed consent is obtained from eligible, volunteering patients, baseline measurements will be administrated, and the patient will be allocated to either sham or active iTBS once a day for 10 consecutive workdays. A total of three measurements will take place, namely at baseline prior to iTBS treatment, after two weeks with iTBS treatment (posttest) and four weeks after (follow-up). The primary outcome measures will be assessed from baseline to the posttest.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Per M Aslaksen, PhD; Phone Number: +47 77649234; Email: per.aslaksen@unn.no
• Study Contact Backup: Name: Marte C Ørbo, PhD; Phone Number: +47 77645333; Email: marte.c.orbo@uit.no

Study Locations

• Norway
  • Tromsø, Norway, 9038
    • Recruiting
    • University Hospital North Norway
    • Contact: Ole Grønli, MD, PhD; Email: ole.k.gronli@unn.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Patients must meet the diagnostic criteria of at least a moderate depression
• The duration of the current depressive episode must have lasted more than 2 weeks but less than 2 years
• Drug therapy must have been stable for the last three weeks prior to the first treatment day with iTBS
• Patients must volunteer to provide informed consent, be able to follow the treatment schedule and have a satisfactory safety screening for iTBS and MRI

Exclusion criteria:

• The current depressive episode is in the mild range
• The current episode fulfills the criteria for a major depressive episode requiring inpatient treatment and/or electroconvulsive therapy,
• The current depressive episode is clearly triggered by grief or a recent major stressful life event
• Bipolar disorder
• Borderline personality disorder
• Psychotic symptoms
• Alcohol or substance abuse/addiction in the last 6 months
• Current eating disorders
• Obsessive- compulsive disorders
• Post-traumatic stress disorder
• A life-time medical history of seizure
• Neurological or neurosurgical pathologies
• Cardiac or systemic disease
• Metallic prosthetic material or foreign objects (pacemakers, prosthetic eye equipment, etc.)
• Autism
• Pregnancy
• Currently using of antipsychotic medication or benzodiazepines - or any medication that interferes with motor threshold excitability

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: Intermittent Theta Burst Stimulation; Stimulation will be performed with a Mag & More PowerMag EEG 100 system with a double PMD70 p-cool (fluid-cooled) figure-of-eight coil.	Device: Intermittent Theta Burst Stimulation; Intermittent Theta Burst Stimulation will be delivered with 120% of resting motor threshold with triplet 50 Hz bursts repeated at 5 Hz; 2 seconds on and 8 s off, 600 pulses per session with a total duration of 3 min 9 s. Treatment will be provided for 10 days for two consecutive weeks (except Saturdays and Sundays).
Placebo Comparator: Sham Intermittent Theta Burst Stimulation; Sham stimulation will be performed by the Mag & More PowerMag EEG 100 system double PMD70 p-cool figure-of-eight coil Sham system.	Device: Intermittent Theta Burst Stimulation; Intermittent Theta Burst Stimulation will be delivered with 120% of resting motor threshold with triplet 50 Hz bursts repeated at 5 Hz; 2 seconds on and 8 s off, 600 pulses per session with a total duration of 3 min 9 s. Treatment will be provided for 10 days for two consecutive weeks (except Saturdays and Sundays).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Data from magnetic resonance imaging - white matter integrity	Differences between groups when comparing intermittent theta burst stimulation versus sham intermittent theta burst stimulation in anatomical measures of cerebral white matter integrity quantified by fractional anisotropy measured by diffusion tensor imaging (DTI) obtained from magnetic resonance imaging (MRI).	Change from the pretest to the posttest after 10 treatments with iTBS, an average of 15 days
Data from magnetic resonance imaging - cortical thickness	Differences between groups when comparing intermittent theta burst stimulation versus sham intermittent theta burst stimulation in anatomical measures of thickness in cerebral gray matter thickness quantified by T1-weighted magnetic resonance imaging (MRI).	Change from the pretest to the posttest after 10 treatments with iTBS, an average of 15 days
Data from magnetic resonance imaging - cerebral activity	Differences between groups when comparing intermittent theta burst stimulation versus sham intermittent theta burst stimulation in cerebral activity quantified by blood-oxygen-level-dependent (BOLD) responses measured by functional resonance imaging (fMRI).	Change from the pretest to the posttest after 10 treatments with iTBS, an average of 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance on a N-back cognitive test	Differences between groups when comparing intermittent theta burst stimulation versus sham intermittent theta burst stimulation in behavioral performance on a cognitive task measuring working memory and executive performance when comparing intermittent theta burst stimulation versus sham intermittent theta burst stimulation.	Change from the pretest to the posttest after 10 treatments with iTBS, an average of 15 days

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Collaborators: UiT The Arctic University of Norway

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): February 12, 2029

Study Registration Dates

• First Submitted: May 25, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 715272

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised data will be made available to other researchers when the study has ended.
• IPD Sharing Time Frame: Data will be published after completion of the study. The study protocol will be published as soon as possible.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

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