Major Depressive EpisodeDREAMSNCT04832750

Depression-Reduction by Accelerated Personalized NeuroModulation and Its Effects on Sleep

An observational study of Major Depressive Episode and Major Depressive Disorder, run by University of Oldenburg at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Episode, Major Depressive Disorder, Borderline Personality Disorder
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 102 participants
Where: 1 siteGermany
Study dates: 3 May 2021to 26 Jul 2024
How long will I take part?: 6 Weeks
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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Study population: Patients at the Department of Psychiatry, University of Oldenburg. The patients' diagnosis of MDD and BPD will be verified via the structured clinical interview for DSM-V. Healthy controls will be matched to the patient sample.

Who may be able to join

Participant is able to provide consent.
Diagnosis of major depressive disorder (MDD) according to DSM-V criteria.
During the current episode, treatment-resistant MDD (at least one failed pharmacological trial of adequate dose and duration)
For the MDD group with comorbid borderline personality disorder (BPD): diagnosis of BPD according to the Diagnotic Statistical Manual V (DSM-V) criteria.
For healthy controls: no psychiatric or neurological illness.

Who cannot join

For the MDD group without BPD: BPD diagnosis
The participant does not fulfill requirements for iTBS treatment according to safety guidelines.
The participant does not fulfill requirements for MRI measurements according to safety guidelines.
Pregnancy or breast-feeding.
Acute suicidality.
Neurological illness (e.g. dementia, Parkinson's disease, chorea huntington, multiple sclerosis).

Show all 10Show fewer

increased current risk for epileptic seizure.
comorbid diagnosis of schizophrenia or psychotic symptoms, bipolar disorder, and substance use disorder within the last 6 months.
Conditions related to increased intracranial pressure.
Brain injury or stroke.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Department of Psychiatry, University of Oldenburg
Bad Zwischenahn, 26160

Other trials in Germany

About this study

Advances in repetitive transcranial magnetic stimulation (rTMS) protocols with intermittent theta-burst stimulation (iTBS) have significantly decreased the duration for one single session and thereby enabled accelerated treatment plans with multiple sessions per day, potentially reducing the total treatment duration. This randomized, placebo-controlled study investigates the effects of accelerated iTBS treatment with connectivity-informed neuronavigation on symptom severity, sleep, interoception, and cognitive control in patients with major depressive disorder and with or without comorbid borderline personality disorder using magnetic resonance imaging (MRI).

Read the detailed description

Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious treatment option for treatment-resistant depression. Advances in rTMS protocols with intermittent theta-burst stimulation (iTBS) have significantly decreased the duration for one single session and thereby enabled accelerated treatment plans with multiple sessions per day, potentially reducing the total treatment duration. Major depressive disorder (MDD) is characterized by impairments in various domains including sleep, impulse control, and interoception. Borderline personality disorder (BPD) is characterized by fear of abandonment, mood swings, and an unstable perception of self and often occurs with comorbid MDD. This comorbidity frequently impedes treatment of the BPD.

In this randomized, placebo-controlled study, 60 patients with treatment-resistant MDD (30 verum group, 30 sham group) and 60 patients with treatment-resistant MDD and comorbid BPD (30 verum group, 30 sham group) will receive two weeks of connectivity-informed iTBS of the left dorsolateral prefrontal cortex (DLPFC; 3 sessions per day, 5 days per week). Before and after the treatment phase, (functional) magnetic resonance imaging (fMRI) will be performed. The effects of iTBS will be tested in four domains: (1) symptom severity (MDD and BPD symptoms), (2) sleep quality (sleep questionnaires and various sleep parameters monitored via an electroencephalography (EEG) headband), (3) neurocognitive effects (vigilance and response inhibition measured with behavioral and fMRI tasks), and (4) interoception (interoceptive attention measured with behavioral and fMRI tasks). Furthermore, before the start of the two-weeks treatment, a single iTBS session ("forecaster session") will be conducted to explore the validity of early symptom/mood responses and hormonal changes for the prediction of the the treatment outcome. Treatment effects will be analyzed within and across patient groups (MDD and MDD + BPD). In addition, domain-specific treatment effects will be analyzed as a function of distinct iTBS targets within the DLPFC.To evaluate pathological biases, the investigators will compare the patients' data with a control group of 30 healthy participants who will also be tested twice (without iTBS).

Conditions: Major Depressive Episode, Major Depressive Disorder, Borderline Personality Disorder
Being tested: intermittent theta burst stimulation (iTBS) or sham stimulation
Keywords: rTMS, Theta Burst Stimulation, Neuronavigation, Major Depressive Episode, Borderline Personality Disorder, Sleep, Interoception, Cognitive Control, fMRI
Medical subject headings: Depressive Disorder, Major, Borderline Personality Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

intermittent theta burst stimulation (iTBS) or sham stimulationDevice
30 sessions of iTBS over 2 weeks (3 sessions per day, 5 days per week)

Study groups in NCT04832750
Study group	Role	What they receive
Major Depressive Episode		At least one failed pharmaco trial in current episode Receives: Device: intermittent theta burst stimulation (iTBS) or sham stimulation
Major Depressive Episode with comorbid Borderline Personality Disorder		At least one failed pharmaco trial in current episode Receives: Device: intermittent theta burst stimulation (iTBS) or sham stimulation
Healthy Controls		No psychiatric disorders

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in depression severity after the treatment phase
Measured with the Montgomery Asberg Rating Scale (MARDS). Remission defined as MADRS score (range: 0 to 60) of less than or equal to 10. Response defined as a reduction of at least 50 percent from baseline in MADRS score.
Measured: Up to 5 weekdays after the last iTBS treatment session
Change in BPD severity after the treatment phase
Measured by the Zanarini rating scale for BPD (Zan-BPD, range 0-36). Remission is defined as score of 9 or less. Response defined as a decrease from baseline in Zan-BPD score of at least 20 percent of the scoring range, i.e. a reduction of 8 points or more.
Measured: Up to 5 weekdays after the last iTBS treatment session
Changes in neural responses in an interoception task before the first and after the last treatment session
Measured with functional magnetic resonance imaging (fMRI) while performing an interoception task
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in neural responses in a cognitive control task before the first and after the last treatment session
Measured with functional magnetic resonance imaging (fMRI) while performing a cognitive control task
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in behavioral responses in an interoception task before the first and after the last treatment session
Measured as performance in an interoception task during fMRI
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in behavioral responses in a cognitive control task before the first and after the last treatment session
Measured as performance in a cognitive control task during fMRI
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in sleep staging over the treatment course
electroencephalography (EEG)-based sleep staging measured with a headband device with accelerometer and pulseoximeter
Measured: 2 days of baseline measurement before the first iTBS session, daily over the treatment course for 10 days

Secondary outcomes (10)

Changes in brain connectivity measures
Structural and functional connectivity measured with MRI including graph measures
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in vigilance over the treatment course
Vigilance measured by Psychomotor Vigilance Task (PVT)
Measured: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days
Changes in symptom severity over treatment course
Measured by the MADRS
Measured: Baseline immediately before the first iTBS session, after 1 week of treatment, after 2 weeks of treatment, and at the follow-up 6 weeks after treatment
Changes in self-reported symptom severity over treatment course and at follow-up
measured by the Beck Depression Inventory (BDI-II)
Measured: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at the follow-up
Changes in Cortisol Awakening Response (CAR) from saliva concentrations
3 measurements after awakening (0,20, and 40 minutes)
Measured: Up to 5 weekdays before the first and after the last treatment session
Changes in blood parameters
Pro- and anti-inflammatory cytokines, and growth factors
Measured: Before the first and after the last treatment session
Association between changes induced by the Forecaster session and treatment outcome
Changes in biomarkers before and after the forecaster iTBS session
Measured: Immediately before and after the forecaster iTBS session
Changes in self-reported BPD symptom severity over treatment course and at follow-up
Measured by the Borderline Symptom List (BSL-23) (range 0-4)
Measured: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at follow-up
Changes in BPD symptom severity over treatment course and at follow-up
Measured by Zan-BPD
Measured: Baseline immediately before the first iTBS session, after 1 week of treatment, and after 2 weeks of treatment
Changes in food craving
Measured by a behavioral food craving task
Measured: Up to 5 weekdays before the first and after the last treatment session

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 May 202126 Jul 2024

First posted6 Apr 2021
Study start3 May 2021
Primary completion14 Jun 2024
Study completion26 Jul 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Major Depressive EpisodeStudies 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: 102 participants (actual)
Target duration: 6 Weeks

IDs, dates and publications

ClinicalTrials.gov ID: NCT04832750
Sponsor's protocol ID: DREAMS
Acronym: DREAMS
Status last verified: Dec 2024
First submitted: 26 Mar 2021
Last updated: 11 Dec 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

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.
PubMed 29726344
Franzen PL, Buysse DJ. Sleep disturbances and depression: risk relationships for subsequent depression and therapeutic implications. Dialogues Clin Neurosci. 2008;10(4):473-81. doi: 10.31887/DCNS.2008.10.4/plfranzen.
PubMed 19170404
Mutz 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 30917990
Rock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014 Jul;44(10):2029-40. doi: 10.1017/S0033291713002535. Epub 2013 Oct 29.
PubMed 24168753
Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry. 2005 Oct;66(10):1254-69. doi: 10.4088/jcp.v66n1008.
PubMed 16259539

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Evaluation of the Acceptability, Feasibility and Exploration of the Efficacy of an Integrated Care Pathway CARIBOU
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French Minds Cohort: a French Longitudinal and Multimodal Cohort of Patients With Major Mood Disorders, Psychotic Disorders, Autism Spectrum Disorders, and Healthy Controls
Schizophrenia / Schizoaffective Disorder, First Episode Psychosis (FEP)
RecruitingPhase 1
Remote Medical Monitoring of Patients With Depression
Depression Chronic, Depression and Quality of Life

All Major Depressive Episode trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Depression-Reduction by Accelerated Personalized NeuroModulation and Its Effects on Sleep
ClinicalTrials.gov ID: NCT04832750
Acronym / sponsor ID: DREAMS / DREAMS
Conditions: Major Depressive Episode, Major Depressive Disorder, Borderline Personality Disorder
Keywords: rTMS, Theta Burst Stimulation, Neuronavigation, Major Depressive Episode, Borderline Personality Disorder, Sleep, Interoception, Cognitive Control
Study type: Observational
Recruitment status: Completed
Enrolment: 102 participants (actual)
Lead sponsor: University of OldenburgUniversity, hospital or other
Collaborators: Marc Onken, M.Sc., Christina Mueller, M.Sc.
Study start: 3 May 2021 (actual)
Primary completion: 14 Jun 2024 (actual)
Study completion: 26 Jul 2024 (actual)
First posted: 6 Apr 2021 (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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Target follow-up: 6 Weeks
Number of arms: 3

Arm	Type	Receives
Major Depressive Episode	–	Device: intermittent theta burst stimulation (iTBS) or sham stimulationAt least one failed pharmaco trial in current episode
Major Depressive Episode with comorbid Borderline Personality Disorder	–	Device: intermittent theta burst stimulation (iTBS) or sham stimulationAt least one failed pharmaco trial in current episode
Healthy Controls	–	–No psychiatric disorders

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult
Study population: Patients at the Department of Psychiatry, University of Oldenburg. The patients' diagnosis of MDD and BPD will be verified via the structured clinical interview for DSM-V. Healthy controls will be matched to the patient sample.

Key inclusion criteria (5 listed)

Participant is able to provide consent.
Diagnosis of major depressive disorder (MDD) according to DSM-V criteria.
During the current episode, treatment-resistant MDD (at least one failed pharmacological trial of adequate dose and duration)
For the MDD group with comorbid borderline personality disorder (BPD): diagnosis of BPD according to the Diagnotic Statistical Manual V (DSM-V) criteria.
For healthy controls: no psychiatric or neurological illness.

Key exclusion criteria (10 listed)

For the MDD group without BPD: BPD diagnosis
The participant does not fulfill requirements for iTBS treatment according to safety guidelines.
The participant does not fulfill requirements for MRI measurements according to safety guidelines.
Pregnancy or breast-feeding.
Acute suicidality.

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) or sham stimulation30 sessions of iTBS over 2 weeks (3 sessions per day, 5 days per week)	Device	Major Depressive Episode, Major Depressive Episode with comorbid Borderline Personality Disorder

Primary outcome

Change in depression severity after the treatment phase
Time frame: Up to 5 weekdays after the last iTBS treatment session
Measured with the Montgomery Asberg Rating Scale (MARDS). Remission defined as MADRS score (range: 0 to 60) of less than or equal to 10. Response defined as a reduction of at least 50 percent from baseline in MADRS score.
Change in BPD severity after the treatment phase
Time frame: Up to 5 weekdays after the last iTBS treatment session
Measured by the Zanarini rating scale for BPD (Zan-BPD, range 0-36). Remission is defined as score of 9 or less. Response defined as a decrease from baseline in Zan-BPD score of at least 20 percent of the scoring range, i.e. a reduction of 8 points or more.
Changes in neural responses in an interoception task before the first and after the last treatment session
Time frame: Up to 5 weekdays before the first and after the last treatment session
Measured with functional magnetic resonance imaging (fMRI) while performing an interoception task
Changes in neural responses in a cognitive control task before the first and after the last treatment session
Time frame: Up to 5 weekdays before the first and after the last treatment session
Measured with functional magnetic resonance imaging (fMRI) while performing a cognitive control task
Changes in behavioral responses in an interoception task before the first and after the last treatment session
Time frame: Up to 5 weekdays before the first and after the last treatment session
Measured as performance in an interoception task during fMRI
Changes in behavioral responses in a cognitive control task before the first and after the last treatment session
Time frame: Up to 5 weekdays before the first and after the last treatment session
Measured as performance in a cognitive control task during fMRI
Changes in sleep staging over the treatment course
Time frame: 2 days of baseline measurement before the first iTBS session, daily over the treatment course for 10 days
electroencephalography (EEG)-based sleep staging measured with a headband device with accelerometer and pulseoximeter

10 secondary outcomes

Changes in brain connectivity measures
Time frame: Up to 5 weekdays before the first and after the last treatment session
Changes in vigilance over the treatment course
Time frame: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days
Changes in symptom severity over treatment course
Time frame: Baseline immediately before the first iTBS session, after 1 week of treatment, after 2 weeks of treatment, and at the follow-up 6 weeks after treatment
Changes in self-reported symptom severity over treatment course and at follow-up
Time frame: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at the follow-up
Changes in Cortisol Awakening Response (CAR) from saliva concentrations
Time frame: Up to 5 weekdays before the first and after the last treatment session
Changes in blood parameters
Time frame: Before the first and after the last treatment session
Association between changes induced by the Forecaster session and treatment outcome
Time frame: Immediately before and after the forecaster iTBS session
Changes in self-reported BPD symptom severity over treatment course and at follow-up
Time frame: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at follow-up
Changes in BPD symptom severity over treatment course and at follow-up
Time frame: Baseline immediately before the first iTBS session, after 1 week of treatment, and after 2 weeks of treatment
Changes in food craving
Time frame: Up to 5 weekdays before the first and after the last treatment session

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
Background: PubMed 29726344Blumberger 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.
Background: PubMed 19170404Franzen PL, Buysse DJ. Sleep disturbances and depression: risk relationships for subsequent depression and therapeutic implications. Dialogues Clin Neurosci. 2008;10(4):473-81. doi: 10.31887/DCNS.2008.10.4/plfranzen.
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 24168753Rock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014 Jul;44(10):2029-40. doi: 10.1017/S0033291713002535. Epub 2013 Oct 29.
Background: PubMed 16259539Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry. 2005 Oct;66(10):1254-69. doi: 10.4088/jcp.v66n1008.
Individual participant dataSharing planned: Undecided

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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.

René Hurlemann, Prof. principal investigator

Department of Psychiatry, University of Oldenburg

Dirk Scheele, Dr. principal investigator

Department of Psychiatry, University of Oldenburg

Christina Mueller, M.Sc. study director

Department of Psychiatry, University of Oldenburg

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 Episode and Major Depressive Disorder, run by University of Oldenburg 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 5 inclusion and 10 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: finished, as of the sponsor's last update on 11 Dec 2024. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in depression severity after the treatment phase (time frame: Up to 5 weekdays after the last iTBS treatment session). The study lists 7 primary outcomes in all. 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 NCT04832750, which also lists 5 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 11 Dec 2024.