Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression

NCT ID: NCT04998773

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-15
• Study Completion Date: 2025-02-28

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)

Conditions

Resistant Depression, Treatment; Bipolar Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group Bilateral

32 patients, bilateral active TBS stimulation, Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Continuous TBS in right DLPFC

Group Type: ACTIVE_COMPARATOR

Theta Burst Transcranial Magnetic Bilateral Stimulation

Intervention Type: DEVICE

TMS protocol of 22 sessions of bilateral active 1800 pulses.

Group Unilateral

32 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 Type: ACTIVE_COMPARATOR

Theta Burst Transcranial Magnetic Unilateral Stimulation

Intervention Type: DEVICE

TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.

Group Placebo

32 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

Group Type: PLACEBO_COMPARATOR

Theta Burst Transcranial Magnetic Sham Stimulation

Intervention Type: DEVICE

TMS protocol of 22 sessions of sham bilateral 1800 pulses.

Interventions

Theta Burst Transcranial Magnetic Bilateral Stimulation

TMS protocol of 22 sessions of bilateral active 1800 pulses.

Intervention Type: DEVICE

Theta Burst Transcranial Magnetic Sham Stimulation

TMS protocol of 22 sessions of sham bilateral 1800 pulses.

Intervention Type: DEVICE

Theta Burst Transcranial Magnetic Unilateral Stimulation

TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Agency of Medicines and Health Products

OTHER_GOV

Sponsor Role: collaborator

Hospital Universitario La Fe

OTHER

Sponsor Role: collaborator

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Instituto de Investigacion Sanitaria La Fe

OTHER

Sponsor Role: lead

Responsible Party

Pilar Sierra Sanmiguel

Principal Investigator, Leader of Mental Health Investigation Group

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pilar Sierra San Miguel, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigación Sanitaria La Fe

Locations

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Yolanda Cañada, MD

Role: CONTACT

canyada_yol@gva.es

+34961244154

Facility Contacts

Yolanda Cañada, MD

Role: primary

canyada_yol@gva.es

+961244154

References

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.

Reference Type: BACKGROUND

PMID: 29726344 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31477542 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24817188 (View on PubMed)

Other Identifiers

PI 2022-280-1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

21-0040

Identifier Type: OTHER

Identifier Source: secondary_id

2021-326-1

Identifier Type: -

Identifier Source: org_study_id