Stepped Care AiTBS 2 Depression Study (Ghent)

NCT ID: NCT03288675

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-05
• Study Completion Date: 2023-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active aiTBS - active CCT+SSRI

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)

Group Type: ACTIVE_COMPARATOR

aiTBS

Intervention Type: 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.

CCT

Intervention Type: 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.

SSRI

Intervention Type: DRUG

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

Active aiTBS - sham CCT+SSRI

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)

Group Type: EXPERIMENTAL

aiTBS

Intervention Type: 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.

SSRI

Intervention Type: DRUG

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

Sham aiTBS - aiTBS - active CCT+SSRI

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)

Group Type: EXPERIMENTAL

aiTBS

Intervention Type: 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.

CCT

Intervention Type: 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.

SSRI

Intervention Type: DRUG

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

Sham aiTBS - aiTBS - sham CCT+SSRI

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)

Group Type: EXPERIMENTAL

aiTBS

Intervention Type: 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.

SSRI

Intervention Type: DRUG

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

Interventions

aiTBS

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.

Intervention Type: DEVICE

CCT

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.

Intervention Type: BEHAVIORAL

SSRI

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

Intervention Type: DRUG

Other Intervention Names

accelerated intermittent thetaburst stimulation; cognitive control training; selective serotonin reuptake inhibitor

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Depression with bipolar/psychotic features
• Dysthymia
• Severe personality disorders
• Active substance abuse/dependence within a year prior to inclusion
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Baeken, Prof.

Role: PRINCIPAL_INVESTIGATOR

Ghent University, University Hospital Ghent

Ernst Koster, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Rudi De Raedt, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Gilles Pourtois, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Marie-Anne Vanderhasselt, Prof.

Role: PRINCIPAL_INVESTIGATOR

Ghent University, University Hospital Ghent

Locations

University Hospital Ghent

Ghent, East-Flanders, Belgium

Countries

Belgium

Other Identifiers

BC-1812

Identifier Type: -

Identifier Source: org_study_id