Investigating Predictors of Treatment Response in Treatment-Resistant Depression (TRD) With Interleaved TMS/fMRI

NCT ID: NCT03642522

Last Updated: 2021-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2020-08-01

Brief Summary

The purpose of this trial is identify biomarkers of response to repetitive transcranial magnetic stimulation (rTMS) in individuals with first episode or treatment resistant depression. These biomarkers include simultaneous TMS-fMRI (functional magnetic resonance imaging), a blood smear, cognitive and behavioural assessments, questionnaires, and neurophysiology.

Detailed Description

This study is enrolling 60 individuals with treatment-resistant depression.

All patients will receive four weeks of 1-Hz rTMS to the right dorsolateral prefrontal cortex (R_DLPFC). In addition, all patients will undergo baseline and post-treatment measures, including rTMS while they are in the MRI scanner, neurophysiology (Electroencephalography (EEG)/Near-Infrared Spectroscopy (NIRS)), cognitive testing, behavioural assessments and a blood smear. There will also be a 1-week, 4-week, and 12-week follow-up following completion of the treatment course.

Conditions

Major Depressive Disorder; Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 Hz rTMS

30 minutes of 1 Hz rTMS to the right dorsolateral prefrontal cortex (R\_DLPFC)

Group Type: EXPERIMENTAL

repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

rTMS is a Health-Canada- and FDA-approved treatment for treatment-resistant depression (TRD), using focused magnetic field pulses to stimulate brain regions involved in emotion regulation, safely and non-invasively. rTMS can be applied at varying discharge frequencies which have differential effects on cortical excitability. At a low frequency (≤ 1Hz), rTMS reduces cortical excitability, while at frequencies greater than 1 Hz, rTMS facilitates cortical excitability3. In MDD, either high- frequency rTMS (HF-rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) or low- frequency rTMS (LF-rTMS) applied over the right DLPFC have similar efficacy. This study utilizes low frequency rTMS to the right DLPFC.

Interventions

repetitive transcranial magnetic stimulation

rTMS is a Health-Canada- and FDA-approved treatment for treatment-resistant depression (TRD), using focused magnetic field pulses to stimulate brain regions involved in emotion regulation, safely and non-invasively. rTMS can be applied at varying discharge frequencies which have differential effects on cortical excitability. At a low frequency (≤ 1Hz), rTMS reduces cortical excitability, while at frequencies greater than 1 Hz, rTMS facilitates cortical excitability3. In MDD, either high- frequency rTMS (HF-rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) or low- frequency rTMS (LF-rTMS) applied over the right DLPFC have similar efficacy. This study utilizes low frequency rTMS to the right DLPFC.

Intervention Type: DEVICE

Other Intervention Names

rTMS

Eligibility Criteria

Inclusion Criteria

Patients will be included if they:

1. are outpatients

2. are voluntary and competent to consent to treatment

3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent

4. are between the ages of 18 and 80 years

5. have failed to achieve a clinical response to at least one adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of score ≥ 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2)

6. have a score ≥ 22 on the IDS item

7. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to initiation of rTMS

8. able to adhere to the treatment schedule

9. pass the TMS adult safety screening (TASS) questionnaire

Patients will be included if they:

1. are outpatients

2. are voluntary and competent to consent to treatment

3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent

4. are between the ages of 18 and 80 years

5. have never received and adequate antidepressant trial and are not currently taking any antidepressant.

6. have a score ≥ 12 on the IDS item

7. are on no psychotropic medication for the 4 weeks prior to initiation of rTMS, with the exception of lorazepam up to 2mg or equivalent dose of benzodiazepine or prescribed sleeping aids including (zopiclone up to 15mg/d, zolpidem up to 10mg/d).

8. able to adhere to the treatment schedule

9. pass the TMS adult safety screening (TASS) questionnaire

Participants will be included if they:

1. are voluntary and competent to consent to the study

2. are between the ages of 18 and 80

3. are fluent in English, sufficient to complete interviews and cognitive testing

4. have no history of Axis I or Axis II disorders, as determined by the MINI

5. pass the TMS adult safety screening (TASS) questionnaire

Exclusion Criteria

Patients are excluded if they:

1. have a history of substance dependence or abuse within the last 3 months

2. have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump

3. have active suicidal intent

4. are pregnant

5. have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms

6. have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD

7. have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD

8. have failed a course of ECT in the current episode or previous episode

9. have received rTMS for any previous indication due to the potential compromise of expectancy effects

10. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes

11. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed

12. If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study

13. have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators

14. are currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) or any dose of an anticonvulsant, due to the potential to limit rTMS efficacy

15. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

16. have failed more than 5 adequate trials of medication in the current episode.

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Participants will be excluded if they:

1. have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms

2. have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), dysthymia or any personality disorder

3. have history of bipolar disorder or psychosis in first degree relative (parents, siblings, offspring)

4. are unable to provide family history of biological family (i.e., adopted persons are not eligible)

5. have a history of substance dependence within the last 3 months

6. have a concomitant major unstable medical illness

7. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes

8. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

9. have a personal or family history of seizures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Victoria

OTHER

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Fidel Vila-Rodriguez

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fidel Vila-Rodriguez, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Non-Invasive Neurostimulation Therapies lab, University of British Columbia

Vancouver, British Columbia, Canada

Countries

Canada

References

Ge R, Humaira A, Gregory E, Alamian G, MacMillan EL, Barlow L, Todd R, Nestor S, Frangou S, Vila-Rodriguez F. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial. Am J Psychiatry. 2022 Jul;179(7):500-508. doi: 10.1176/appi.ajp.21050541. Epub 2022 May 18.

Reference Type: DERIVED

PMID: 35582784 (View on PubMed)

Other Identifiers

H14-02819

Identifier Type: -

Identifier Source: org_study_id