Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression (EMTtfNI)

February 21, 2024 updated by: Pilar Sierra Sanmiguel, Instituto de Investigacion Sanitaria La Fe

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Spain
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitario y Politécnico La Fe
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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
Device: Theta Burst Transcranial Magnetic Bilateral Stimulation
TMS protocol of 22 sessions of bilateral active 1800 pulses.
Active Comparator: 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
Device: Theta Burst Transcranial Magnetic Unilateral Stimulation
TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.
Placebo Comparator: 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
Device: Theta Burst Transcranial Magnetic Sham Stimulation
TMS protocol of 22 sessions of sham bilateral 1800 pulses.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.
Time Frame: 6 weeks
Hetero-administered
6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Beck Depression Inventory (BDI-II) respect to basal.
Time Frame: 2, 6 weeks
Self-administered
2, 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.
Time Frame: 2, 6 weeks
Hetero-administered
2, 6 weeks
Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.
Time Frame: 2, 6 weeks
Hetero-administered
2, 6 weeks
Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.
Time Frame: 2, 6 weeks
Self-administered
2, 6 weeks
Clinical Global Impression Scale (CGI) respect to basal.
Time Frame: 2,6 weeks
Hetero-administered
2,6 weeks
Hamilton Anxiety Scale (HAM-A) respect to basal.
Time Frame: 2,6 weeks
Hetero-administered
2,6 weeks
Oviedo Sleep Questionnaire (OSQ) respect to basal.
Time Frame: 2, 6 weeks
Hetero-administered
2, 6 weeks
Dimensional Apathy Scale (DAS) respect to basal
Time Frame: 6 weeks
Self-administered
6 weeks
Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.
Time Frame: 6 weeks
Hetero-administered (versions A and B)
6 weeks
Short Form Health Survey (SF 36) at the end of the treatment respect to basal.
Time Frame: 6 weeks
Self-administered
6 weeks
Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.
Time Frame: 6 weeks
Hetero-administered
6 weeks
Global assessment of Functioning (GAF) at the end of the treatment respect to basal.
Time Frame: 6 weeks
Hetero-administered
6 weeks
Response to treatment
Time Frame: 2 and 6 weeks
50% reduction in HDRS-17
2 and 6 weeks
Response to treatment
Time Frame: 2 and 6 weeks
50% reduction in MADRS
2 and 6 weeks
Remission
Time Frame: 2 and 6 weeks
HDRS-17<8 points
2 and 6 weeks
Remission
Time Frame: 2 and 6 weeks
MADRS<11 POINTS
2 and 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Investigacion Sanitaria La Fe

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Instituto de Salud Carlos III
Hospital Universitario La Fe
Spanish Agency of Medicines and Health Products

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Pilar Sierra San Miguel, PhD, Instituto de Investigación Sanitaria La Fe

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 2, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 10, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 22, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2021-326-1
  • PI 2022-280-1 (Other Grant/Funding Number: Carlos III Health Institute)
  • 21-0040 (Other Identifier: AEMPS, NEOPS code)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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