Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression
EMTtfNI
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
3 other identifiers
interventional
96
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Sep 2021
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 2, 2021
CompletedFirst Posted
Study publicly available on registry
August 10, 2021
CompletedStudy Start
First participant enrolled
September 15, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2025
CompletedFebruary 22, 2024
February 1, 2024
3.4 years
August 2, 2021
February 21, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.
Hetero-administered
6 weeks
Secondary Outcomes (16)
Beck Depression Inventory (BDI-II) respect to basal.
2, 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.
2, 6 weeks
Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.
2, 6 weeks
Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.
2, 6 weeks
Clinical Global Impression Scale (CGI) respect to basal.
2,6 weeks
- +11 more secondary outcomes
Study Arms (3)
Group Bilateral
ACTIVE COMPARATOR32 patients, bilateral active TBS stimulation, Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Continuous TBS in right DLPFC
Group Unilateral
ACTIVE COMPARATOR32 patients, unilateral left DLPFC active TBS stimulation. Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Sham Continuous TBS in right DLPFC
Group Placebo
PLACEBO COMPARATOR32 patients, bilateral sham TBS stimulation. Will receive an intensive-spaced protocol of Sham Intermittent TBS in left DLPFC and Sham Continuous TBS in right DLPFC
Interventions
TMS protocol of 22 sessions of bilateral active 1800 pulses.
TMS protocol of 22 sessions of sham bilateral 1800 pulses.
TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.
Eligibility Criteria
You may qualify if:
- Diagnosis of Major Depressive Episode or Depressive phase in Bipolar Disorder DSM-5 criteria.
- Moderate severity (\>14 points in HDRS)
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Instituto de Investigacion Sanitaria La Felead
- Spanish Agency of Medicines and Health Productscollaborator
- Hospital Universitario La Fecollaborator
- Instituto de Salud Carlos IIIcollaborator
Study Sites (1)
Hospital Universitario y Politécnico La Fe
Valencia, 46026, Spain
Related Publications (3)
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.
PMID: 29726344BACKGROUNDFitzgerald 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.
PMID: 31477542BACKGROUNDLi 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.
PMID: 24817188BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pilar Sierra San Miguel, PhD
Instituto de Investigación Sanitaria La Fe
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator, Leader of Mental Health Investigation Group
Study Record Dates
First Submitted
August 2, 2021
First Posted
August 10, 2021
Study Start
September 15, 2021
Primary Completion
February 1, 2025
Study Completion
February 28, 2025
Last Updated
February 22, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will not share