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

Major Depressive Disorder Clinical Trial

— DREAMS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04832750
• Other study ID #: DREAMS
• Status: Recruiting
• Start date: May 3, 2021
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: University of Oldenburg
• Contact: René Hurlemann, Prof.
• Phone: +49 (0)441 9615
• Email: rene.hurlemann[@]uni-oldenburg.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

• 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.

Related Conditions & MeSH terms

• Borderline Personality Disorder
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Major Depressive Episode
• Personality Disorders

Intervention

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

Locations

Country	Name	City	State
Germany	Department of Psychiatry, University of Oldenburg	Bad Zwischenahn

Sponsors (3)

Lead Sponsor	Collaborator
University of Oldenburg	Christina Mueller, M.Sc., Marc Onken, M.Sc.

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. Erratum In: Lancet. 2018 Jun 23;391(10139):e24. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry. 2005 Oct;66(10):1254-69. doi: 10.4088/jcp.v66n1008. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 weekdays after the last iTBS treatment session
Primary	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.	Up to 5 weekdays after the last iTBS treatment session
Primary	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	Up to 5 weekdays before the first and after the last treatment session
Primary	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	Up to 5 weekdays before the first and after the last treatment session
Primary	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	Up to 5 weekdays before the first and after the last treatment session
Primary	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	Up to 5 weekdays before the first and after the last treatment session
Primary	Changes in sleep staging over the treatment course	electroencephalography (EEG)-based sleep staging measured with a headband device with accelerometer and pulseoximeter	2 days of baseline measurement before the first iTBS session, daily over the treatment course for 10 days
Secondary	Changes in brain connectivity measures	Structural and functional connectivity measured with MRI including graph measures	Up to 5 weekdays before the first and after the last treatment session
Secondary	Changes in vigilance over the treatment course	Vigilance measured by Psychomotor Vigilance Task (PVT)	Baseline immediately before the first iTBS session, daily over the treatment course for 10 days
Secondary	Changes in symptom severity over treatment course	Measured by the MADRS	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
Secondary	Changes in self-reported symptom severity over treatment course and at follow-up	measured by the Beck Depression Inventory (BDI-II)	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
Secondary	Changes in Cortisol Awakening Response (CAR) from saliva concentrations	3 measurements after awakening (0,20, and 40 minutes)	Up to 5 weekdays before the first and after the last treatment session
Secondary	Changes in blood parameters	Pro- and anti-inflammatory cytokines, and growth factors	Before the first and after the last treatment session
Secondary	Association between changes induced by the Forecaster session and treatment outcome	Changes in biomarkers before and after the forecaster iTBS session	Immediately before and after the forecaster iTBS session
Secondary	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)	Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at follow-up
Secondary	Changes in BPD symptom severity over treatment course and at follow-up	Measured by Zan-BPD	Baseline immediately before the first iTBS session, after 1 week of treatment, and after 2 weeks of treatment
Secondary	Changes in food craving	Measured by a behavioral food craving task	Up to 5 weekdays before the first and after the last treatment session