The Antidepressant Effect of Intermittent Theta Burst Stimulation (iTBS)

The Antidepressant Effect of Intermittent Theta Burst Stimulation (iTBS) A Randomised Double-blind Sham-controlled Trial

The present study is a randomized placebo-controlled trial examining the effect of intermittent theta burst stimulation (iTBS) on unipolar depression. iTBS is a form of transcranial magnet stimulation.

The anti-depressive effect of two weeks of once- a - day neuronavigated iTBS over the dorsolateral left prefrontal cortex (DLPFC) will be investigated in comparison to sham (placebo) iTBS. Previous studies have shown that iTBS is an effective treatment for reducing symptoms of depression, but it is still unclear why some patients have a strong response to iTBS, whereas others show less or no reduction to test possible factors that can explain the inter-individual response to iTBS.

Measures of cognitive functions, structural and functional brain data measured by Magnetic Resonance imaging (MRi), quality of life, sleep quality, general health status, and genetic measures will be obtained to answer the goals of this study.

The main hypotheses are: 1) Patients receiving iTBS will display significantly larger reductions in depressive symptoms measured by the Montgomery-Asberg Depression Rating Scale and Becks Depression Inventory II compared to patients receiving sham stimulation. 2) Reduction in depressive symptoms will be significantly associated with a concomitant improvement in executive functions measured by neuropsychological tests. 3) Stronger connectivity at baseline between the DLFPC and the anterior cingulate cortices will be associated with better response to iTBS. 4) Variability in genetic measures will be significantly associated with treatment response to iTBS. 5) Variability in white matter structural measures of the brain will be significantly associated with the anti-depressive response to iTBS.

Participants will be recruited prospectively, and the study 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. Four weeks after the last treatment day, the patients will be followed up by phone interviews.

Study Overview

• Status: Recruiting
• Conditions: Depression; Executive Dysfunction
• Intervention / Treatment: Device: Transcranial magnet stimulation; Device: Sham Transcranial magnet stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Per M Aslaksen, PhD; Phone Number: 4777649234; Email: per.aslaksen@uit.no
• Study Contact Backup: Name: Marte C Ørbo, PhD; 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
    • Contact: Camilla Larsen, MD; Email: cal023@post.uit.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A MADRS score of =/ > 20 (moderate depression).
• 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 and is to be kept stable throughout the study until 4 weeks after the last day of iTBS treatment.
• 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 or contrary that 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 the last 6 months.
• Alcohol or substance abuse/addiction in the last 6 months.
• Current eating disorders.
• Obsessive- compulsive disorders.
• Post-traumatic stress disorder.
• Any medical history of seizure.
• Any neurological or neurosurgical pathologies.
• Any current cardiac or systemic disease.
• Metallic prosthetic material or foreign objects in the body (pacemakers, internal cardioverter defibrillator units, insulin pump, prosthetic eye equipment, etc.).
• Previously diagnosed developmental disorder.
• Pregnancy or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active iTBS; iTBS will be delivered with 120% of resting motor threshold, 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). Each patient will start treatment at the same time between 9 am and 3 pm during the 10-day treatment period.	Device: Transcranial magnet stimulation; Theta burst stimulation, which is a form of Transcranial magnet stimulation, works by inducing focused magnetic field pulses to make durable changes in the activity of brain regions. The magnetic pulses are transferred to the brain through an electromagnetic coil.; Other Names: Theta burst stimulation
PLACEBO_COMPARATOR: Sham iTBS; The sham system has an identical look, weight and sound compared to the true coil, and delivers electrical stimulation that can be felt at the skin but without penetrating the skull and thus not inducing any treatment effect. The sham stimulation will be given with the same procedure as the active stimulation; 2 seconds on and 8 s off, 600 pulses per session with a total duration of 3 min 9 s.	Device: Sham Transcranial magnet stimulation; Similar in appearance and give the same sound as the active device, but deliver no magnetic pulse that reach the brain; Other Names: Sham Theta burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale.	Clinician rated depression inventory.	Up to 4 months.
Beck's Depression Inventory - II.	Patient reported depression inventory.	Up to 4 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck's Anxiety Inventory.	Patient reported anxiety inventory.	Up to 4 months.
Wisconsin Card Sorting Test.	Performance based measure of executive functions.	Up to 2 weeks.
Delis-Kaplan Executive Function System.	Performance based measure of executive functions.	Up to 2 weeks.
Brief-A	Questionnaire for self-reported executive functioning.	Up to 4 months.
Whodas 2.0	Self-reported disability assessment schedule.	Up to 4 months.
Pittsburgh Sleep Quality Index.	Self-reported measure of sleep quality.	Up to 4 months.

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Collaborators: UiT The Arctic University of Norway
• Investigators: Principal Investigator: Per M Aslaksen, PhD, UiT The Arctic University of Norway; Principal Investigator: Marte C Ørbo, PhD, UiT The Arctic University of Norway; Principal Investigator: Ole Grønli, MD, PhD, University Hospital North Norway

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 4, 2022
• Primary Completion (ANTICIPATED): May 31, 2025
• Study Completion (ANTICIPATED): December 31, 2027

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: August 22, 2022
• First Posted (ACTUAL): August 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: major depression; moderate depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 228765; HNF1578-21 (OTHER_GRANT: Northern Norway Regional Health Authorithy)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data for outcome measures in the study.
• IPD Sharing Time Frame: Data used for publications in peer-reviewed journals will be shared after publication at the open data platform used at UiT the Arctic University of Norway.
• IPD Sharing Access Criteria: Open for everyone.
• IPD Sharing Supporting Information Type: SAP; 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