Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression

Bipolar Depression Clinical Trial

— EMTtfNI  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04998773
• Other study ID #: 2021-326-1
• Secondary ID: PI 2022-280-121-
• Status: Recruiting
• Phase: N/A
• Start date: September 15, 2021
• Est. completion date: February 28, 2025

Study information

• Verified date: February 2024
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: Yolanda Cañada, MD
• Phone: +34961244154
• Email: canyada_yol[@]gva.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: February 28, 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

Device:
• Theta Burst Transcranial Magnetic Bilateral Stimulation
TMS protocol of 22 sessions of bilateral active 1800 pulses.
• Theta Burst Transcranial Magnetic Sham Stimulation
TMS protocol of 22 sessions of sham bilateral 1800 pulses.
• Theta Burst Transcranial Magnetic Unilateral Stimulation
TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.

Locations

Country	Name	City	State
Spain	Hospital Universitario y Politécnico La Fe	Valencia

Sponsors (4)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe	Hospital Universitario La Fe, Instituto de Salud Carlos III, Spanish Agency of Medicines and Health Products

Country where clinical trial is conducted

Spain, 

References & 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. Erratum In: Lancet. 2018 Jun 23;391(10139):e24. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.	Hetero-administered	6 weeks
Secondary	Beck Depression Inventory (BDI-II) respect to basal.	Self-administered	2, 6 weeks
Secondary	Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.	Hetero-administered	2, 6 weeks
Secondary	Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.	Hetero-administered	2, 6 weeks
Secondary	Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.	Self-administered	2, 6 weeks
Secondary	Clinical Global Impression Scale (CGI) respect to basal.	Hetero-administered	2,6 weeks
Secondary	Hamilton Anxiety Scale (HAM-A) respect to basal.	Hetero-administered	2,6 weeks
Secondary	Oviedo Sleep Questionnaire (OSQ) respect to basal.	Hetero-administered	2, 6 weeks
Secondary	Dimensional Apathy Scale (DAS) respect to basal	Self-administered	6 weeks
Secondary	Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.	Hetero-administered (versions A and B)	6 weeks
Secondary	Short Form Health Survey (SF 36) at the end of the treatment respect to basal.	Self-administered	6 weeks
Secondary	Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.	Hetero-administered	6 weeks
Secondary	Global assessment of Functioning (GAF) at the end of the treatment respect to basal.	Hetero-administered	6 weeks
Secondary	Response to treatment	50% reduction in HDRS-17	2 and 6 weeks
Secondary	Response to treatment	50% reduction in MADRS	2 and 6 weeks
Secondary	Remission	HDRS-17<8 points	2 and 6 weeks
Secondary	Remission	MADRS<11 POINTS	2 and 6 weeks