Clinical trial NCT04832750: Depression-Reduction by Accelerated Personalized NeuroModulation and Its Effects on Sleep
Official title: Depression-Reduction by Accelerated Personalized NeuroModulation and Its Effects on Sleep
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
fMRI
Lead sponsor: University of Oldenburg
Sponsor class: OTHER
Collaborators: name: Marc Onken, M.Sc.
name: Christina Mueller, M.Sc.
First posted: 2021-04-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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).

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in depression severity after the treatment phase
timeFrame: Up to 5 weekdays after the last iTBS treatment session
measure: Change in BPD severity after the treatment phase
timeFrame: Up to 5 weekdays after the last iTBS treatment session
measure: Changes in neural responses in an interoception task before the first and after the last treatment session
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in neural responses in a cognitive control task before the first and after the last treatment session
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in behavioral responses in an interoception task before the first and after the last treatment session
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in behavioral responses in a cognitive control task before the first and after the last treatment session
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in sleep staging over the treatment course
timeFrame: 2 days of baseline measurement before the first iTBS session, daily over the treatment course for 10 days
Secondary outcomes:
measure: Changes in brain connectivity measures
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in vigilance over the treatment course
timeFrame: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days
measure: Changes in symptom severity over treatment course
timeFrame: 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
measure: Changes in self-reported symptom severity over treatment course and at follow-up
timeFrame: 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
measure: Changes in Cortisol Awakening Response (CAR) from saliva concentrations
timeFrame: Up to 5 weekdays before the first and after the last treatment session
measure: Changes in blood parameters
timeFrame: Before the first and after the last treatment session
measure: Association between changes induced by the Forecaster session and treatment outcome
timeFrame: Immediately before and after the forecaster iTBS session
measure: Changes in self-reported BPD symptom severity over treatment course and at follow-up
timeFrame: Baseline immediately before the first iTBS session, daily over the treatment course for 10 days, 6 weeks after last iTBS session at follow-up
measure: Changes in BPD symptom severity over treatment course and at follow-up
timeFrame: Baseline immediately before the first iTBS session, after 1 week of treatment, and after 2 weeks of treatment
measure: Changes in food craving
timeFrame: Up to 5 weekdays before the first and after the last treatment session
Other outcomes:
Locations:
city: Bad Zwischenahn
country: Germany
facility: Department of Psychiatry, University of Oldenburg
Study officials:
affiliation: Department of Psychiatry, University of Oldenburg
name: René Hurlemann, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry, University of Oldenburg
name: Dirk Scheele, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry, University of Oldenburg
name: Christina Mueller, M.Sc.
role: STUDY_DIRECTOR
affiliation: Department of Psychiatry, University of Oldenburg
name: Marc Onken, M.Sc.
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
citation: Tsuno N, Besset A, Ritchie K. Sleep and depression. J Clin Psychiatry. 2005 Oct;66(10):1254-69. doi: 10.4088/jcp.v66n1008.