Stepped Care AiTBS 2 Depression Study (Ghent)

NCT03288675 | Completed

• 1 other identifier: BC-1812
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Antidepressant-free unipolar melancholic depressed patients (at least stage 2 treatment-resistant) will be selected by a certified psychiatrist, who will administer (semi-)structured clinical interviews. Because concomitant antidepressant treatment can confound outcome results, all patients will go through a medication washout before entering the study and they will be free from any antidepressant, neuroleptic and mood stabilizer for at least two weeks before entering the treatment protocol. Only habitual benzodiazepine agents will be allowed. STEP 1: Patients will be treated with in total 20 accelerated intermittent Theta Burst Stimulation (aiTBS) sessions (3000 pulses/session) over the left dorsolateral prefrontal cortex, which will be spread over 4 days. On each stimulation day, a given patient will receive 5 sessions with a between-session delay of 15 minutes. Patients will be randomized to receive either the real aiTBS or sham treatment (first week). However, the sham group will receive real aiTBS treatment with 10 days' time interval. The investigators expect that real aiTBS treatment and not sham will result in a significant and clinical meaningful response. STEP 2: To optimize treatment and reduce relapse following the iTBS treatment, in a stepped care approach, all patients then continue with cognitive control training (CCT) ten days later. This CCT consists of 20 sessions, spread over 4 weeks. Patients will be randomized to receive either real CCT or a control training. During this follow-up treatment, all patients will be prescribed antidepressant medication (SSRI) again. As iTBS treatment effects are known to decline over time, the investigators expect that combining aiTBS with a follow-up CCT therapy will stabilize the clinical effects over time compared to receiving the iTBS treatment alone. For baseline comparisons, patients will be closely matched for gender and age with never-depressed, medication-free healthy volunteers. No volunteer will undergo treatment.

Conditions

Depressive Disorder, Major; Treatment Resistant Depression; Melancholia

Keywords

Major depressive disorder; Treatment resistant depression; Accelerated intermittent thetaburst stimulation; Cognitive control training; Neuroimaging

Outcome Measures

Primary Outcomes (1)

• Changes in depression severity - clinician-rated

  17-item Hamilton Rating Scale for Depression (HRSD)

  Intake, baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

Secondary Outcomes (30)

• Changes in depression severity - self-report

  Intake, baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

• Changes in suicidal thoughts - clinician-rated

  Intake, baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

• Changes in melancholic features - clinician-rated

  Intake, baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

• Changes in hopelessness - self-report

  Baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

• Changes in anxiety features - self-report

  Baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14), [for the sham group 3 days (+/-D21) and 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up

Study Arms (4)

Active aiTBS - active CCT+SSRI

ACTIVE COMPARATOR

Patients receive active aiTBS treatment in the first week, and starting from week 3 receive active CCT for a period of 4 weeks in combination with an antidepressant (SSRI)

Device: aiTBS; Behavioral: CCT; Drug: SSRI

Active aiTBS - sham CCT+SSRI

EXPERIMENTAL

Patients receive active aiTBS treatment in the first week, and starting from week 3 receive a control training for a period of 4 weeks in combination with an antidepressant (SSRI)

Device: aiTBS; Drug: SSRI

Sham aiTBS - aiTBS - active CCT+SSRI

EXPERIMENTAL

Patients receive sham aiTBS treatment in the first week, real aiTBS treatment in the third week, and starting from the fifth week receive CCT for a period of 4 weeks in combination with an antidepressant (SSRI)

Device: aiTBS; Behavioral: CCT; Drug: SSRI

Sham aiTBS - aiTBS - sham CCT+SSRI

EXPERIMENTAL

Patients receive sham aiTBS treatment in the first week, real aiTBS treatment in the third week, and starting from the fifth week control training for a period of 4 weeks in combination with an antidepressant (SSRI)

Device: aiTBS; Drug: SSRI

Interventions

aiTBS DEVICE

In the active aiTBS arm, the patients will receive 100 cycli of thetaburst trains of 2s, separated by an inter-train-interval of 6 seconds, delivered on the left dorsolateral prefrontal cortex (DLPFC; i.e. 3000 pulses per session). On each stimulation day, a given patient will receive 5 sessions with a between-session interval of 15 minutes. The treatment protocol of in total 20 aiTBS sessions will be spread over 4 days (i.e. 60.000 pulses in total). The sham coil has been specifically developed to mimic the real one.

Also known as: accelerated intermittent thetaburst stimulation

Active aiTBS - active CCT+SSRI; Active aiTBS - sham CCT+SSRI; Sham aiTBS - aiTBS - active CCT+SSRI; Sham aiTBS - aiTBS - sham CCT+SSRI

CCT BEHAVIORAL

By training working memory processing, the CCT aims at modulating similar prefrontal cortex regions as being stimulated previously by aiTBS, namely the DLPFC. thereby possibly stabilizing clinical effects of aiTBS over time. In total 20 sessions of CCT vs. control training (of approximately 25 minutes per session), will be spread over a period of 4 weeks.

Also known as: cognitive control training

Active aiTBS - active CCT+SSRI; Sham aiTBS - aiTBS - active CCT+SSRI

SSRI DRUG

All patients will be prescribed antidepressant medication (SSRI) again when starting the CCT (vs. control training).

Also known as: selective serotonin reuptake inhibitor

Active aiTBS - active CCT+SSRI; Active aiTBS - sham CCT+SSRI; Sham aiTBS - aiTBS - active CCT+SSRI; Sham aiTBS - aiTBS - sham CCT+SSRI

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Antidepressant-free unipolar major depression with melancholic features
• Not responding to at least two trials with an antidepressant
• Aged between 18-65 years old

You may not qualify if:

• Depression with bipolar/psychotic features
• Dysthymia
• Severe personality disorders
• Pregnancy or without effective anticonception for the duration of the trial
• ECT non-responder
• No response to more than 9 antidepressants
• Any neurological condition
• Any implanted electronic device susceptible for magnetic field radiation (e.g. pacemaker)
• Any implanted metal device in the head region
• Current or past history of epilepsy
• Neurosurgical interventions
• Known allergic reaction to radiotracers or associated compounds
• Healthy volunteers may be accepted as control subjects.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

University Hospital Ghent

Ghent, East-Flanders, 9000, Belgium

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Depressive Disorder

Interventions

Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Study Officials

• Chris Baeken, Prof.

  Ghent University, University Hospital Ghent

  PRINCIPAL INVESTIGATOR

• Ernst Koster, Prof.

  University Ghent

  PRINCIPAL INVESTIGATOR

• Rudi De Raedt, Prof.

  University Ghent

  PRINCIPAL INVESTIGATOR

• Gilles Pourtois, Prof.

  University Ghent

  PRINCIPAL INVESTIGATOR

• Marie-Anne Vanderhasselt, Prof.

  Ghent University, University Hospital Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: September 20, 2017
• Study Start: October 5, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)