Resting-state Functional Connectivity Throughout a Course of iTBS in Major Depression

NCT03944213 | Unknown

• 1 other identifier: DepRest
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate changes in functional connectivity over a four week treatment course with intermittent theta burst stimulation (iTBS) in patients with major depressive disorder (MDD). To this end, seven weekly resting-state fMRI (rs-fMRI) scans at 7 tesla (7T) will precede, accompany and follow the iTBS treatment course. By obtaining several samples of the modulatory effects of iTBS on functional connectivity networks and simultaneous measurements of the depressive symptoms it will be possible to assess the time course of changes in connectivity across different networks, and to assess the overall relationship between the network modulation and the antidepressant effects of the treatment over time.

Conditions

Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Episode

Keywords

Transcranial Magnetic Stimulation; Theta Burst Stimulation; rTMS; TBS; resting-state fMRI

Outcome Measures

Primary Outcomes (1)

• Change in functional connectivity coefficients based on rs-fMRI over 7 timepoints.

  Seed-to-voxel functional connectivity analysis of rs-fMRI data.

  Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement.

Secondary Outcomes (1)

• Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints.

  Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement.

Study Arms (2)

MDD patients

Device: intermittent theta burst stimulation (iTBS)

Healthy controls

Interventions

intermittent theta burst stimulation (iTBS) DEVICE

20 sessions of iTBS

MDD patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Outpatients at the psychiatric hospital of the University Hospital Bonn. The patients diagnosis of major depressive disorder will be verified via the structured clinical interview for DSM-5. iTBS protocols in line with international standards administered by a trained professional. Additionally, a healthy control sample is included in the study.

You may qualify if:

• Participant is able to provide consent.
• Diagnosis of Major Depressive Disorder according to DSM-V criteria.
• The duration of the current episode is at least four weeks and no more than five years.
• During the current episode, at least one antidepressant (adequate duration and dosage) was not effective OR at least two antidepressants were intolerable due to side effects.

You may not qualify if:

• The participant does not fulfill requirements for iTBS treatment according to safety guidelines.
• Cardiac or neurological surgery, active implants, metal parts within the body, claustrophobia.
• Pregnancy or breast-feeding.
• Psychiatric illness, e.g. substance abuse, psychosis, bipolar disorder, anorexia, obsessive compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, personality disorder.
• Antipsychotic medication not approved for the treatment of depression.
• Acute suicidality.
• Conditions related to increased intracranial pressure.
• Brain injury or stroke.
• History of epilepsy in patient or in first-degree relative.
• Cerebral aneurysm.
• Neurological illness (e.g. dementia (score of less than 25 in Mini Mental State Exam), Parkinson's disease, chorea huntington, multiple sclerosis).
• Course of electroconvulsive therapy (ECT) within the last three months

Sponsors & Collaborators

• University Hospital, Bonn: lead
• Clemens Mielacher, University Hospital, Bonn: collaborator
• Maximilian Kiebs, University Hospital, Bonn: collaborator

Study Sites (1)

Klinik und Poliklinik für Psychiatrie und Psychotherapie

Bonn, Germany

RECRUITING

Related Publications (11)

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  PMID: 17074942 BACKGROUND

• Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry. 2006;67 Suppl 6:16-22.

  PMID: 16848672 BACKGROUND

• Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry. 2010 Oct;9(3):155-61. doi: 10.1002/j.2051-5545.2010.tb00298.x.

  PMID: 20975857 BACKGROUND

• Kaiser RH, Andrews-Hanna JR, Wager TD, Pizzagalli DA. Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity. JAMA Psychiatry. 2015 Jun;72(6):603-11. doi: 10.1001/jamapsychiatry.2015.0071.

  PMID: 25785575 BACKGROUND

• Fischer AS, Keller CJ, Etkin A. The Clinical Applicability of Functional Connectivity in Depression: Pathways Toward More Targeted Intervention. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 May;1(3):262-270. doi: 10.1016/j.bpsc.2016.02.004. Epub 2016 Mar 2.

  PMID: 29560882 BACKGROUND

• Liston C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ. Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014 Oct 1;76(7):517-26. doi: 10.1016/j.biopsych.2014.01.023. Epub 2014 Feb 5.

  PMID: 24629537 BACKGROUND

• Philip NS, Barredo J, van 't Wout-Frank M, Tyrka AR, Price LH, Carpenter LL. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Biol Psychiatry. 2018 Feb 1;83(3):263-272. doi: 10.1016/j.biopsych.2017.07.021. Epub 2017 Aug 8.

  PMID: 28886760 BACKGROUND

• Berlim MT, van den Eynde F, Tovar-Perdomo S, Daskalakis ZJ. Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol Med. 2014 Jan;44(2):225-39. doi: 10.1017/S0033291713000512. Epub 2013 Mar 18.

  PMID: 23507264 BACKGROUND

• Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.

  PMID: 29726344 BACKGROUND

• Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.

  PMID: 25034472 BACKGROUND

• Hale JR, Brookes MJ, Hall EL, Zumer JM, Stevenson CM, Francis ST, Morris PG. Comparison of functional connectivity in default mode and sensorimotor networks at 3 and 7T. MAGMA. 2010 Dec;23(5-6):339-49. doi: 10.1007/s10334-010-0220-0. Epub 2010 Jul 13.

  PMID: 20625794 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Study Officials

• René Hurlemann, Prof.

  University Hospital, Bonn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clemens Mielacher, Mag.

CONTACT

+49 228 287 11519; clemens.mielacher@ukbonn.de

Maximilian Kiebs, M.Sc.

CONTACT

+49 228 287 19710; m.kiebs@ukbonn.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of the Medical Psychology Division and Deputy Chair of the Department of Psychiatry

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 9, 2019
• Study Start: July 23, 2018
• Primary Completion: February 1, 2023
• Study Completion: June 1, 2024
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)