Multisite rTMS for Mood, Cognitive Impairment and Other Symptoms of Depression

Multisite Repetitive Transcranial Magnetic Stimulation for Mood, Cognitive Impairment, Anhedonia and Disordered Sleep in Depressive Disorder

Depressed mood is the main symptom of depression, but other symptoms like cognitive impairment, anhedonia or sleep disorders may also contribute to patients suffering and are difficult to treat. rTMS is a relatively novel treatment option, whose therapeutic potential is still investigated and optimized. The aim of this study is to assess the effect of rTMS applied over two stimulation sites on cognitive impairment, anhedonia and sleep disorders in depression.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder; Unipolar Depression
• Intervention / Treatment: Device: Active rTMS over the left DLPFC and over the left DMPFC; Device: Active rTMS over the left DLPFC; Device: Sham rTMS

Detailed Description

Depression is one of the most common and disabling disorders, affecting approximately three hundred million people worldwide. Depressive mood is the main symptom, but other symptoms like cognitive impairment, anhedonia or sleep disorders contribute significantly to patients suffering, decrease quality of life and may even lead to suicide attempt. While modern pharmacotherapy can significantly improve symptoms in many patients, still one third of patients remains drug-resistant. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of inducing brain plasticity. Stimulation over the left and right dorsolateral prefrontal cortex (DLPFC) and possibly over several other areas can improve mood. Only few studies investigated the effect of rTMS on negative psychiatric symptoms, such as anhedonia, sleeplessness or cognitive impairment. In these trials, either the DLPFC or the dorsomedial prefrontal cortex (dmPFC) were stimulated and sometimes other areas such as the insular cortex. The aim of this study is to investigate if a stimulation over both sites (multi-site stimulation) has better therapeutic potential for depressed mood, cognitive impairment, anhedonia and sleep disorders than stimulation over DLPFC alone and placebo.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wojciech Korzeniowski, MD; Phone Number: +48 12 652 45 20; Email: wojciech.korzen@gmail.com
• Study Contact Backup: Name: Jakub Antczak, MD; Phone Number: +48 12 400 25 50; Email: jakub.antczak@uj.edu.pl

Study Locations

• Poland
  • Cracovia, Poland, 30393
    • Recruiting
    • The Education of Research and Development Center, Babinski Clinical Hospital
    • Contact: Wojciech Korzeniowski, MD; Phone Number: +48 12 652 42 00; Email: wojciech.korzen@gmail.com
    • Contact: Jakub Antczak, MD; Phone Number: +48 12 25 50; Email: jakub.antczak@uj.edu.pl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• severe or moderate depressive episode (according to international classification of diseases (ICD)-10) without psychotic symptoms at the time of inclusion
• Hamilton Depression Rating Scale between between 20 and 35 points at inclusion
• The score in the Athens Insomnia Scale eight or more
• The score of three or more points in items 4 and 21 of the Beck Depressions Inventory 2
• Complaining about problems with memory and concentration timely related with the onset of depression

Exclusion Criteria:

• Contraindications to transcranial magnetic stimulation, including ferromagnetic elements in head, pregnancy and epilepsy
• Psychotic symptoms at the time of inclusion
• Suicidal ideations and/or attempts within three months prior to inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS over the left DLPFC and over the left DMPFC; Active 10 Herz rTMS with intensity of 120% of the resting motor threshold recorded from the right first dorsal interosseus and the right abductor hallucis will be administered over the left DLPFC and over the left DMPFC respectively. Therapy will include 20 sessions (one session in each of 20 consecutive working days - four weeks in total). In every session ca 1500 magnetic pulses over the left DLPFC and ca 1500 over the left DMPFC will be elicited.	Device: Active rTMS over the left DLPFC and over the left DMPFC; Active rTMS over the left DLPFC and over the left DMPFC to induce the long term potentiation of stimulated areas.
Active Comparator: rTMS over the left DLPFC; Active 10 Herz rTMS with intensity of 120% of the resting motor threshold recorded from the right first dorsal interosseus will be administered over the left DLPFC. Therapy will include 20 sessions (one session in each of 20 consecutive working days - four weeks in total). In every session 3000 magnetic pulses over the left DLPFC will be elicited.	Device: Active rTMS over the left DLPFC; Active rTMS over the left DLPFC to induce the long term potentiation of stimulated area.
Sham Comparator: Sham rTMS; Sham 10 Herz rTMS will be administered over the left DLPFC. Therapy will include 20 sessions (one session in each of 20 consecutive working days - four weeks in total). In every session 3000 magnetic pulses over the left DLPFC or ca 1500 magnetic pulses over the left DLPFC and ca 1500 over the left DMPFC will be elicited. (rTMS protocol will be chosen randomly before the first session).	Device: Sham rTMS; Sham rTMS over the left DLPFC or over the left DLPFC and over the left DMPFC for placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory 2	Inventory consisting of 21 items measuring cognitive, affective, somatic, and vegetative symptoms of depression. Each item is scored from 0 to 3, with a higher score denoting more severe depression. Items are related to the criteria from the Diagnostic and Statistical Manual of Mental Disorders-IV. The minimum value of the total score is 0 and the maximum is 63 with higher scores meaning worse outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.
Froward digit span	A measure of verbal short term and working memory. Participant is asked to repeat the random series of numbers, which become longer along with every correctly repeated one. Test is finished after participant failed to respond correctly on three occasions. The number of correctly repeated series determines the final score, which is an integer representing the length of the largest passed sequence. The scores range from 3 to 9 with higher scores denoting better outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.
Language part of Addenbrooke's Cognitive Examination	A test to identify cognitive impairment in dementia. In the language part, participant is asked to complete a set commands such as "place the paper on top of the pencil"; to write grammatically-complete sentences; to repeat several words and proverbs; to name the objects shown in drawings, and answer questions and to read several mispronounced words. The number of correctly completed tasks is scored. The minimum value of the total score is 0 and the maximum (of the language part) is 26 with higher scores meaning better outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dimensional Anhedonia Rating Scale	A 17-item scale that measures desire, motivation, effort and consummatory pleasure across hedonic domains. In each item, participant chooses one of four statements describing his attitude towards a given activity. The minimum value of the total score is 0 and the maximum is 68 with higher scores meaning better outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.
Athens Insomnia Scale	An eight item scale. Each item is rated from 0 to 3 with higher scores representing more severe insomnia. Change from baseline score in the Athens Insomnia Scale to the measurement taken after finishing rTMS. The minimum value of the total score is 0 and the maximum is 24 with higher scores meaning worse outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.
Pittsburgh Sleep Quality Index	Pittsburgh Sleep Quality Index (PSQI) is a questionnaire to identify sleep disturbances. It consists of a combination of Likert-type and open-ended questions, which are later converted to scaled scores. Scores for each question range from 0 to 3. The minimum value of the total score is 0 and the maximum is 21 with higher scores meaning worse outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.
Epworth Sleepiness Scale	An eight-item scale. Each item refers to a situation such as driving a car or sitting quietly. The subject is asked to assess the chance of dosing in each situation, ranging from 0 (no chance) to 3 (dosing very likely). The minimum value of the total score is 0 and the maximum is 24 with higher scores meaning worse outcome. Change from the baseline to the measurement done after finishing intervention, to the measurement done two weeks after finishing intervention to the measurement done four weeks after finishing intervention.	Before intervention - four weeks after finishing intervention.

Collaborators and Investigators

• Sponsor: Jakub Antczak
• Collaborators: Andrzej Frycz Modrzewski Krakow University
• Investigators: Principal Investigator: Wojciech Korzeniowski, MD, The Education of Research and Development Center, Babinski Clinical Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: depression; repetitive transcranial magnetic stimulation; cognitive impairment; sleep disorders; dorsolateral prefrontal cortex; anhedonia; dorsomedial prefrontal cortex
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Neurocognitive Disorders; Cognition Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Cognitive Dysfunction; Bipolar Disorder
• Other Study ID Numbers: JagiellonianU72

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Scans of scales, inventories and questionnaires will be available upon request sent per e-mail to: wojciech.korzen@gmail.com
• IPD Sharing Time Frame: December 2026 - December 2030
• IPD Sharing Access Criteria: For researchers in medical sciences and medical professional upon justification of their request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No