Clinical trial NCT04998773: Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression
Official title: Efficacy, Clinical and Neuroimaging Biomarkers of Response of Two Intensive/Spaced Protocols of Theta-Burst Transcranial Magnetic Stimulation in Resistant Depression: a Randomized Double-blinded Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Resistant Depression, Treatment
Bipolar Depression
Keywords: TMS
iTBS
Depression
Bipolar depression
Antidepressants
Neuroimaging
PET-MRI
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
Collaborators: name: Spanish Agency of Medicines and Health Products
name: Hospital Universitario La Fe
name: Instituto de Salud Carlos III
First posted: 2021-08-10
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Theta Burst Transcranial Magnetic Stimulation (TBS) in dorsolateral prefrontal cortex (DLPFC) has shown efficacy and safety as an adjuvant strategy for resistant to treatment depression (RTD) in daily sessions during 4-6 weeks (20-30 sessions). Current investigation in TBS aims to design intensive treatment protocols so as to achieve earlier responses and higher rates of efficacy. However, the implementation of TBS in the Public National Health Service requires cost-effective protocols that ensure and facilitate patients adherence to treatment, and whose design is based on clinical and neuroimaging biomarkers of response so as to adequately select candidate patients. The aim of this study is to assess the efficacy and safety of novel bilateral and unilateral intensive and spaced protocols of TBS in outpatients with unipolar and bipolar RTD compared with sham stimulation. Specific objectives: I) Comparison of mood change, response and remission of depressive illness at the end of TBS protocol in the groups and maintenance of its effect at 3 months; II) Characterization of neuroimaging cerebral connectivity networks and cerebral metabolism patterns of patients with RTD related to the effects of bilateral or unilateral TBS; III) Identification of clinical and demographic predictors contributing to response to TBS; IV) Analysis of the interaction between clinical, demographic and neuroimaging predictors so as to determine a RTD profile of patient that can benefit from TBS.

Detailed description: Participants will receive 22 bilateral sessions of sham/active continuous (right DLPFC) and intermittent (left DLPFC) TBS during 6 weeks. Simultaneous cerebral PET-MRI will be performed before (week 0) and after the treatment with TBS (week 7)

* Weeks 1 and 2: 1 session 5 days a week (10 sessions)
* Weeks 3,4,5, 6: 1 session 3 days a week (12 sessions)

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Major Depressive Episode or Depressive phase in Bipolar Disorder DSM-5 criteria.
* Moderate severity (\>14 points in HDRS)
* 2 antidepressant failures or failure in enhancing strategies in the case of bipolar depression.
* No changes in treatment 3 week previous to the onset of treatment with TMS.
* Ability to sign informed consent.

Exclusion Criteria:

* Any psychiatric comorbidity in axis I or II.
* Depressive episode with psychotic features.
* Dysthymia.
* Treatment with ECT in current depressive episode.
* Multiresistance (\> 6 trials of therapeutic strategies).
* Suicide risk assessed previous to each session.
* Patients who miss 2 TMS sessions in a row
* Neurological comorbidities (epilepsy, Parkinson disease, neurocognitive disorders).
* Contraindications to TMS: pregnancy, metallic cervical or head implants.

Primary outcomes:
measure: Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.
timeFrame: 6 weeks
Secondary outcomes:
measure: Beck Depression Inventory (BDI-II) respect to basal.
timeFrame: 2, 6 weeks
measure: Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.
timeFrame: 2, 6 weeks
measure: Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.
timeFrame: 2, 6 weeks
measure: Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.
timeFrame: 2, 6 weeks
measure: Clinical Global Impression Scale (CGI) respect to basal.
timeFrame: 2,6 weeks
measure: Hamilton Anxiety Scale (HAM-A) respect to basal.
timeFrame: 2,6 weeks
measure: Oviedo Sleep Questionnaire (OSQ) respect to basal.
timeFrame: 2, 6 weeks
measure: Dimensional Apathy Scale (DAS) respect to basal
timeFrame: 6 weeks
measure: Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.
timeFrame: 6 weeks
measure: Short Form Health Survey (SF 36) at the end of the treatment respect to basal.
timeFrame: 6 weeks
measure: Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.
timeFrame: 6 weeks
measure: Global assessment of Functioning (GAF) at the end of the treatment respect to basal.
timeFrame: 6 weeks
measure: Response to treatment
timeFrame: 2 and 6 weeks
measure: Response to treatment
timeFrame: 2 and 6 weeks
measure: Remission
timeFrame: 2 and 6 weeks
measure: Remission
timeFrame: 2 and 6 weeks
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Instituto de Investigación Sanitaria La Fe
name: Pilar Sierra San Miguel, PhD
role: PRINCIPAL_INVESTIGATOR
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: Fitzgerald PB, Chen L, Richardson K, Daskalakis ZJ, Hoy KE. A pilot investigation of an intensive theta burst stimulation protocol for patients with treatment resistant depression. Brain Stimul. 2020 Jan-Feb;13(1):137-144. doi: 10.1016/j.brs.2019.08.013. Epub 2019 Aug 22.
citation: Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, Su TP. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain. 2014 Jul;137(Pt 7):2088-98. doi: 10.1093/brain/awu109. Epub 2014 May 10.