Resistant Depression, TreatmentEMTtfNINCT04998773
Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression
A study testing Theta Burst Transcranial Magnetic Bilateral Stimulation and Theta Burst Transcranial Magnetic Unilateral Stimulation in people with Resistant Depression, Treatment and Bipolar Depression, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Resistant Depression, Treatment, Bipolar Depression
- What is being tested?
- Theta Burst Transcranial Magnetic Bilateral Stimulation and Theta Burst Transcranial Magnetic Unilateral Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteSpain
- Study dates
- 15 Sep 2021to 28 Feb 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario y Politécnico La Fe
Valencia, 46026
Yolanda Cañada, MD, +961244154, canyada_yol@gva.es
About this study
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
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.
Read the 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)
- Being tested
- Theta Burst Transcranial Magnetic Bilateral Stimulation, Theta Burst Transcranial Magnetic Sham Stimulation, Theta Burst Transcranial Magnetic Unilateral Stimulation
- Keywords
- TMS, iTBS, Depression, Bipolar depression, Antidepressants, Neuroimaging, PET-MRI
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theta Burst Transcranial Magnetic Bilateral StimulationDevice
TMS protocol of 22 sessions of bilateral active 1800 pulses.
Theta Burst Transcranial Magnetic Sham StimulationDevice
TMS protocol of 22 sessions of sham bilateral 1800 pulses.
Theta Burst Transcranial Magnetic Unilateral StimulationDevice
TMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses.
| Study group | Role | What they receive |
|---|---|---|
| Group Bilateral | Active comparator | 32 patients, bilateral active TBS stimulation, Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Continuous TBS in right DLPFC Receives: Device: Theta Burst Transcranial Magnetic Bilateral Stimulation |
| Group Unilateral | Active comparator | 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 Receives: Device: Theta Burst Transcranial Magnetic Unilateral Stimulation |
| Group Placebo | Placebo comparator | 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 Receives: Device: Theta Burst Transcranial Magnetic Sham Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.
Hetero-administered
Measured: 6 weeks
Secondary outcomes (16)
Beck Depression Inventory (BDI-II) respect to basal.
Self-administered
Measured: 2, 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.
Hetero-administered
Measured: 2, 6 weeks
Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.
Hetero-administered
Measured: 2, 6 weeks
Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.
Self-administered
Measured: 2, 6 weeks
Clinical Global Impression Scale (CGI) respect to basal.
Hetero-administered
Measured: 2,6 weeks
Hamilton Anxiety Scale (HAM-A) respect to basal.
Hetero-administered
Measured: 2,6 weeks
Oviedo Sleep Questionnaire (OSQ) respect to basal.
Hetero-administered
Measured: 2, 6 weeks
Dimensional Apathy Scale (DAS) respect to basal
Self-administered
Measured: 6 weeks
Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.
Hetero-administered (versions A and B)
Measured: 6 weeks
Short Form Health Survey (SF 36) at the end of the treatment respect to basal.
Self-administered
Measured: 6 weeks
Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.
Hetero-administered
Measured: 6 weeks
Global assessment of Functioning (GAF) at the end of the treatment respect to basal.
Hetero-administered
Measured: 6 weeks
Response to treatment
50% reduction in HDRS-17
Measured: 2 and 6 weeks
Response to treatment
50% reduction in MADRS
Measured: 2 and 6 weeks
Remission
HDRS-17<8 points
Measured: 2 and 6 weeks
Remission
MADRS<11 POINTS
Measured: 2 and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start15 Sep 2021
- Primary completionFeb 2025 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Resistant Depression, TreatmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigacion Sanitaria La Fe
- Sponsor type
- University, hospital or other
- Collaborators
- Spanish Agency of Medicines and Health Products, Hospital Universitario La Fe, Instituto de Salud Carlos III
- Responsible party
- Principal investigator, Pilar Sierra Sanmiguel, Instituto de Investigacion Sanitaria La Fe
- Investigators
- Pilar Sierra San Miguel, PhD, Principal investigator, Instituto de Investigación Sanitaria La Fe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04998773
- Sponsor's protocol ID
- 2021-326-1
- Other IDs
- PI 2022-280-1, 21-0040
- Acronym
- EMTtfNI
- Status last verified
- Feb 2024
- First submitted
- 2 Aug 2021
- Last updated
- 22 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 29726344Fitzgerald 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.
PubMed 31477542Li 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.
PubMed 24817188
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04998773
- Acronym / sponsor ID
- EMTtfNI / 2021-326-1
- Keywords
- TMS, iTBS, Depression, Bipolar depression, Antidepressants, Neuroimaging, PET-MRI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Instituto de Investigacion Sanitaria La FeUniversity, hospital or other
- Collaborators
- Spanish Agency of Medicines and Health Products, Hospital Universitario La Fe, Instituto de Salud Carlos III
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group Bilateral | Active comparator | Device: Theta Burst Transcranial Magnetic Bilateral Stimulation32 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 comparator | Device: Theta Burst Transcranial Magnetic Unilateral Stimulation32 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 comparator | Device: Theta Burst Transcranial Magnetic Sham Stimulation32 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Theta Burst Transcranial Magnetic Bilateral StimulationTMS protocol of 22 sessions of bilateral active 1800 pulses. | Device | Group Bilateral |
| Theta Burst Transcranial Magnetic Sham StimulationTMS protocol of 22 sessions of sham bilateral 1800 pulses. | Device | Group Placebo |
| Theta Burst Transcranial Magnetic Unilateral StimulationTMS protocol of 22 sessions of left active 1800 pulses and right sham 1800 pulses. | Device | Group Unilateral |
Primary outcome
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.
Time frame: 6 weeks
Hetero-administered
16 secondary outcomes
Beck Depression Inventory (BDI-II) respect to basal.
Time frame: 2, 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.
Time frame: 2, 6 weeks
Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.
Time frame: 2, 6 weeks
Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.
Time frame: 2, 6 weeks
Clinical Global Impression Scale (CGI) respect to basal.
Time frame: 2,6 weeks
Hamilton Anxiety Scale (HAM-A) respect to basal.
Time frame: 2,6 weeks
Oviedo Sleep Questionnaire (OSQ) respect to basal.
Time frame: 2, 6 weeks
Dimensional Apathy Scale (DAS) respect to basal
Time frame: 6 weeks
Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.
Time frame: 6 weeks
Short Form Health Survey (SF 36) at the end of the treatment respect to basal.
Time frame: 6 weeks
Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.
Time frame: 6 weeks
Global assessment of Functioning (GAF) at the end of the treatment respect to basal.
Time frame: 6 weeks
Response to treatment
Time frame: 2 and 6 weeks
Response to treatment
Time frame: 2 and 6 weeks
Remission
Time frame: 2 and 6 weeks
Remission
Time frame: 2 and 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
- Background: PubMed 29726344Blumberger 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.
- Background: PubMed 31477542Fitzgerald 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.
- Background: PubMed 24817188Li 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pilar Sierra San Miguel, PhD principal investigator
Instituto de Investigación Sanitaria La Fe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Theta Burst Transcranial Magnetic Bilateral Stimulation and Theta Burst Transcranial Magnetic Unilateral Stimulation in people with Resistant Depression, Treatment and Bipolar Depression, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yolanda Cañada, MD (+34961244154, canyada_yol@gva.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04998773, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.