Major Depressive DisorderNAIVNCT04000022
Repetitive Transcranial Magnetic Stimulation in Pharmaco-naïve Patients With Major Depression
An observational study of Major Depressive Disorder, run by University Hospital, Bonn at 1 site in Germany.
Trial summary
Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression. In several studies investigating the antidepressant efficacy of rTMS, it has been shown that in low treatment-resistant patients rTMS is more efficacious than in patients… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- intermittent theta burst stimulation (iTBS)
- Type of treatment
- Medical device
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2019to 1 May 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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, pharmacological intervention was prescribed (and taken) by the patient
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Klinik und Poliklinik für Psychiatrie und Psychotherapie
Bonn, North Rhine-Westphalia, 53105
Maximilian Kiebs, M.Sc., 0228287 ext. 19710, m.kiebs@ukbonn.de
About this study
Official title: Comparative Efficacy of Repetitive Transcranial Magnetic Stimulation in Pharmaco-naïve and Treatment Resistant Patients With Major Depression
Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression. In several studies investigating the antidepressant efficacy of rTMS, it has been shown that in low treatment-resistant patients rTMS is more efficacious than in patients where several treatment attempts have failed. Albeit this finding, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance and there is a lack of trials investigating rTMS as a first-line treatment. Therefore, this trials aims to compare the antidepressant efficacy of 4 weeks open-label theta-burst TMS in non-treatment-resistant patients with a comparable group of treatment-resistant MDD patients.
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression (Mutz et al., 2019). Consequently, several countries including Australia, Brazil, Canada, Israel and the United States have approved rTMS as second-line treatment for major depressive disorder (MDD), while others have included rTMS in their guidelines for good clinical practice (e.g. Finland, Germany and Serbia). Historically, rTMS was conceptualized as a "soft" alternative to electroconvulsive therapy. Therefore, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance (> two failed treatment attempts) and there is a lack of trials investigating rTMS as a first or second line treatment. This finding is contrasted by the fact that on the most stable predictors of response to rTMS is low-treatment resistance.
Therefore, this trial aims to compare the antidepressant efficacy of 20 pharmaco-naïve patients with 20 treatment-resistant patients diagnosed with major depressive disorder. In this open label trial, patients will receive four weeks high-frequency left-sided theta burst TMS (lDLFPC). The target will be located by neuronavigation to the target ascertained by Fox et al.
- Conditions
- Major Depressive Disorder
- Being tested
- intermittent theta burst stimulation (iTBS)
- Keywords
- Major Depressive Disorder, rTMS, TBS, Theta Burst Stimulation, Neuronavigation, Non-Treatment Resistant, Pharmaco-Naïve
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intermittent theta burst stimulation (iTBS)Device
20 sessions of iTBS
| Study group | Role | What they receive |
|---|---|---|
| Non-Treatment Resistant Patients | Not described Receives: Device: intermittent theta burst stimulation (iTBS) | |
| Treatment-Resistant Patients | The group of patients from NCT03944213 Receives: Device: intermittent theta burst stimulation (iTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints
Remission defined as HDRS-17 score (range: 0 to 52) of less than or equal to 8 after the iTBS course. Response defined as a reduction of at least 50% from baseline in HDRS-17 score after treatment
Measured: Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start1 Jan 2019
- Primary completion29 Dec 2023 (estimated)
- Study completion1 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Collaborators
- Maximilian Kiebs, M.S., Clemens Mielacher, M.S.
- Responsible party
- Principal investigator, Rene Hurlemann, University Hospital, Bonn
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04000022
- Sponsor's protocol ID
- NAIV
- Acronym
- NAIV
- Status last verified
- May 2022
- First submitted
- 25 Jun 2019
- Last updated
- 25 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Fregni F, Marcolin MA, Myczkowski M, Amiaz R, Hasey G, Rumi DO, Rosa M, Rigonatti SP, Camprodon J, Walpoth M, Heaslip J, Grunhaus L, Hausmann A, Pascual-Leone A. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2006 Dec;9(6):641-54. doi: 10.1017/S1461145705006280. Epub 2005 Nov 23.
PubMed 16939662Brakemeier EL, Luborzewski A, Danker-Hopfe H, Kathmann N, Bajbouj M. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J Psychiatr Res. 2007 Aug;41(5):395-403. doi: 10.1016/j.jpsychires.2006.01.013. Epub 2006 Mar 22.
PubMed 16554071Lisanby SH, Husain MM, Rosenquist PB, Maixner D, Gutierrez R, Krystal A, Gilmer W, Marangell LB, Aaronson S, Daskalakis ZJ, Canterbury R, Richelson E, Sackeim HA, George MS. Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology. 2009 Jan;34(2):522-34. doi: 10.1038/npp.2008.118. Epub 2008 Aug 13.
PubMed 18704101Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ. 2019 Mar 27;364:l1079. doi: 10.1136/bmj.l1079.
PubMed 30917990Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
PubMed 22658708Kiebs M, Hurlemann R, Mutz J. Repetitive transcranial magnetic stimulation in non-treatment-resistant depression. Br J Psychiatry. 2019 Aug;215(2):445-446. doi: 10.1192/bjp.2019.75. Epub 2019 Apr 24.
PubMed 31014413
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Efficacy of Repetitive Transcranial Magnetic Stimulation in Pharmaco-naïve and Treatment Resistant Patients With Major Depression
- ClinicalTrials.gov ID
- NCT04000022
- Acronym / sponsor ID
- NAIV / NAIV
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, rTMS, TBS, Theta Burst Stimulation, Neuronavigation, Non-Treatment Resistant, Pharmaco-Naïve
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Collaborators
- Maximilian Kiebs, M.S., Clemens Mielacher, M.S.
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 29 Dec 2023 (estimated)
- Study completion
- 1 May 2024 (estimated)
- First posted
- 27 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression. In several studies investigating the antidepressant efficacy of rTMS, it has been shown that in low treatment-resistant patients rTMS is more efficacious than in patients where several treatment attempts have failed. Albeit this finding, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance and there is a lack of trials investigating rTMS as a first-line treatment. Therefore, this trials aims to compare the antidepressant efficacy of 4 weeks open-label theta-burst TMS in non-treatment-resistant patients with a comparable group of treatment-resistant MDD patients.
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) has become a safe and efficacious treatment for patients with treatment-resistant depression (Mutz et al., 2019). Consequently, several countries including Australia, Brazil, Canada, Israel and the United States have approved rTMS as second-line treatment for major depressive disorder (MDD), while others have included rTMS in their guidelines for good clinical practice (e.g. Finland, Germany and Serbia). Historically, rTMS was conceptualized as a "soft" alternative to electroconvulsive therapy. Therefore, most studies to date primarily recruited patients with relatively high degrees of treatment-resistance (> two failed treatment attempts) and there is a lack of trials investigating rTMS as a first or second line treatment. This finding is contrasted by the fact that on the most stable predictors of response to rTMS is low-treatment resistance.
Therefore, this trial aims to compare the antidepressant efficacy of 20 pharmaco-naïve patients with 20 treatment-resistant patients diagnosed with major depressive disorder. In this open label trial, patients will receive four weeks high-frequency left-sided theta burst TMS (lDLFPC). The target will be located by neuronavigation to the target ascertained by Fox et al.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-Treatment Resistant Patients | – | Device: intermittent theta burst stimulation (iTBS) |
| Treatment-Resistant Patients | – | Device: intermittent theta burst stimulation (iTBS)The group of patients from NCT03944213 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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, pharmacological intervention was prescribed (and taken) by the patient
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intermittent theta burst stimulation (iTBS)20 sessions of iTBS | Device | Non-Treatment Resistant Patients, Treatment-Resistant Patients |
Primary outcome
Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints
Time frame: Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement
Remission defined as HDRS-17 score (range: 0 to 52) of less than or equal to 8 after the iTBS course. Response defined as a reduction of at least 50% from baseline in HDRS-17 score after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2022.
- Background: PubMed 16939662Fregni F, Marcolin MA, Myczkowski M, Amiaz R, Hasey G, Rumi DO, Rosa M, Rigonatti SP, Camprodon J, Walpoth M, Heaslip J, Grunhaus L, Hausmann A, Pascual-Leone A. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2006 Dec;9(6):641-54. doi: 10.1017/S1461145705006280. Epub 2005 Nov 23.
- Background: PubMed 16554071Brakemeier EL, Luborzewski A, Danker-Hopfe H, Kathmann N, Bajbouj M. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J Psychiatr Res. 2007 Aug;41(5):395-403. doi: 10.1016/j.jpsychires.2006.01.013. Epub 2006 Mar 22.
- Background: PubMed 18704101Lisanby SH, Husain MM, Rosenquist PB, Maixner D, Gutierrez R, Krystal A, Gilmer W, Marangell LB, Aaronson S, Daskalakis ZJ, Canterbury R, Richelson E, Sackeim HA, George MS. Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology. 2009 Jan;34(2):522-34. doi: 10.1038/npp.2008.118. Epub 2008 Aug 13.
- Background: PubMed 30917990Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ. 2019 Mar 27;364:l1079. doi: 10.1136/bmj.l1079.
- Background: PubMed 22658708Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
- Background: PubMed 31014413Kiebs M, Hurlemann R, Mutz J. Repetitive transcranial magnetic stimulation in non-treatment-resistant depression. Br J Psychiatry. 2019 Aug;215(2):445-446. doi: 10.1192/bjp.2019.75. Epub 2019 Apr 24.
- Individual participant dataSharing planned: Undecided
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder, run by University Hospital, Bonn at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rene Hurlemann, Prof. (0049228287 ext. 19124, rene.hurlemann@ukbonn.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints (time frame: Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04000022, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2022.