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Stepped Care aiTBS 2 Depression Study (Ghent) (aiTBS2-Ghent)

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ClinicalTrials.gov Identifier: NCT03288675
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : October 6, 2017
Sponsor:
Collaborator:
University Hospital, Ghent
Information provided by (Responsible Party):
University Hospital, Ghent ( University Ghent )

Tracking Information
First Submitted Date  ICMJE July 14, 2017
First Posted Date  ICMJE September 20, 2017
Last Update Posted Date October 6, 2017
Actual Study Start Date  ICMJE October 5, 2017
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
Changes in depression severity - clinician-rated [ Time Frame: 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 ]
17-item Hamilton Rating Scale for Depression (HRSD)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2017)
  • Changes in depression severity - self-report [ Time Frame: 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 ]
    Beck Depression Inventory (BDI-II)
  • Changes in suicidal thoughts - clinician-rated [ Time Frame: 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 ]
    Scale for suicidal ideation (SSI)
  • Changes in melancholic features - clinician-rated [ Time Frame: 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 ]
    Clinical outcomes in routine evaluation (CORE)
  • Changes in hopelessness - self-report [ Time Frame: 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 ]
    Beck hopelessness scale (BHS)
  • Changes in anxiety features - self-report [ Time Frame: 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 ]
    State/Trait Anxiety Inventory (STAI)
  • Changes in remission from depression - self-report [ Time Frame: 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 ]
    Remission from Depression Questionnaire (RDQ)
  • Changes in ruminative thinking (trait) - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Ruminative Responses Scale (RRS)
  • Changes in hedonia - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Temporal Experience of Pleasure Scale (TEPS)
  • Changes in anhedonia - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Snaith-Hamilton Pleasure Scale (SHAPS)
  • Changes in perceived stress - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Perceived Stress Scale (PSS)
  • Changes in responses to positive affect - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Responses to Positive Affect Scale (RPA)
  • Changes in cognitive emotion regulation - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56), 3 & 6 months follow-up ]
    Cognitive Emotion Regulation Questionnaire (CERQ)
  • Changes in temperament and character - self-report [ Time Frame: Intake, 10 days after aiTBS or sham (+/-D14) ]
    Temperament and Character Inventory (TCI)
  • Differences in adverse effects following aiTBS vs. sham - self-report [ Time Frame: 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)] ]
    Adverse effects questionnaire
  • Changes in regional grey matter volume using structural MRI [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    The analysis will be done using voxel-based morphometry
  • Changes in regional white matter microstructure and structural connectivity [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    The analysis will be done using diffusion tensor imaging (DTI)
  • Neuronal safety/ changes in neurometabolite concentrations in left-prefrontal tissues using MRS [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    The analysis will be evaluated using 1H MR spectroscopy
  • Changes in functional activity connectivity at rest and during tasks in which self-referential social evaluations are presented via headphones in the scanner [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    The analysis will be evaluated using resting state and task fMRI
  • Changes in state-dependent ruminative thinking due to hearing self-referential social evaluations presented via headphones in the scanner - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    Before entering the scanner, and following each resting state fMRI (i.e. before hearing self-referential social evaluations and after hearing these evaluations), perseverative thinking will be assessed using the perseverative thinking questionnaire (PTQ).
  • Changes in state-dependent mood due to hearing self-referential social evaluations presented via headphones in the scanner - self-report [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14) ]
    Before entering the scanner, and following each resting state fMRI (i.e. before hearing self-referential social evaluations and after hearing these evaluations), mood will be assessed using visual analogue scales (VAS).
  • Changes in the regional 5-HT transporter system [ Time Frame: Baseline (D0), 3 days after aiTBS or sham (+/-D7), 10 days after aiTBS or sham (+/-D14) ]
    C11 DASB PET
  • Changes in reward processing as measured with EEG /ERP [ Time Frame: Baseline (D0), 10 days after active aiTBS in both groups (+/-D14 for the active group, +/-D28 for the sham group) ]
    128 channel EEG during doors gambling task to assess effects on reward processing.
  • Evaluation of cognitive side-effects following iTBS vs. sham using the CANTAB battery [ Time Frame: Baseline (D0), 3 days after aiTBS or sham (+/-D7) ]
    CANTAB battery administration (i.e. motor screening, delayed matching to sample, rapid visual information processing, one touch stockings of Cambridge, spatial working memory).
  • Changes in reward processing - behavioral assessment [ Time Frame: Baseline (D0), 10 days after aiTBS or sham (+/-D14), [for the sham group 10 days after active aiTBS (+/-D28)], after CCT (+/-D42; for the sham group +/-D56) ]
    Cambridge Gambling Task (CGT; CANTAB battery)
  • Changes in working memory - behavioral assessment of near transfer [ Time Frame: Baseline (D0), 10 days after active aiTBS in both groups (+/-D14 for the active group, +/-D28 for the sham group), after CCT (+/-D42; for the sham group +/-D56) ]
    Non-adaptive PASAT (naPASAT)
  • Changes in state-dependent mood - self-report following naPASAT [ Time Frame: Baseline (D0), 10 days after active aiTBS in both groups (+/-D14 for the active group, +/-D28 for the sham group), after CCT (+/-D42; for the sham group +/-D56) ]
    Visual analogue scales (VAS) administered following completion of the naPASAT
  • Changes in spatial working memory - behavioral assessment of far transfer [ Time Frame: Baseline (D0), 10 days after active aiTBS in both groups (+/-D14 for the active group, +/-D28 for the sham group), after CCT (+/-D42; for the sham group +/-D56) ]
    Spatial working memory (SWT; CANTAB battery)
  • Changes in state-dependent mood during CCT vs. control training [ Time Frame: Following each of the 20 CCT or control trainings (spread over +/- D15 up to D42 for the active group; spread over +/- D29 up to D56 for the sham group) ]
    Visual analogue scales (VAS) administered following completion of the CCT (or control training)
  • Predictive influence of single nucleotide polymorphisms on treatment outcome - genetics using a saliva sample [ Time Frame: At baseline (D0) ]
    SNP analysis
  • Predictive influence of treatment expectancy on treatment response - self-report [ Time Frame: After the first aiTBS or sham session (D1), after the first CCT or control session (+/- D15 for the active group, +/-D29 for the sham group) ]
    Credibility and Expectancy Questionnaire (CEQ)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stepped Care aiTBS 2 Depression Study (Ghent)
Official Title  ICMJE The Effects of Accelerated Intermittent Thetaburst Stimulation Followed by a Cognitive Control Training in Treatment Resistant Unipolar Depressed Patients
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Depressive Disorder, Major
  • Treatment Resistant Depression
  • Melancholia
Intervention  ICMJE
  • Device: 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.
    Other Name: accelerated intermittent thetaburst stimulation
  • Behavioral: 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.
    Other Name: cognitive control training
  • Drug: SSRI
    All patients will be prescribed antidepressant medication (SSRI) again when starting the CCT (vs. control training).
    Other Name: selective serotonin reuptake inhibitor
Study Arms  ICMJE
  • Active Comparator: 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)
    Interventions:
    • Device: aiTBS
    • Behavioral: CCT
    • Drug: SSRI
  • Experimental: 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)
    Interventions:
    • Device: aiTBS
    • Drug: SSRI
  • Experimental: 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)
    Interventions:
    • Device: aiTBS
    • Behavioral: CCT
    • Drug: SSRI
  • Experimental: 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)
    Interventions:
    • Device: aiTBS
    • Drug: SSRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 19, 2017)
68
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Chris Baeken, Prof. +3293325543 Chris.Baeken@ugent.be
Contact: Josefien Dedoncker, M.Sc. +3293325894 Josefien.Dedoncker@ugent.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03288675
Other Study ID Numbers  ICMJE 16/GOA/017
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Ghent ( University Ghent )
Study Sponsor  ICMJE University Ghent
Collaborators  ICMJE University Hospital, Ghent
Investigators  ICMJE
Principal Investigator: 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
PRS Account University Hospital, Ghent
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP