High Dose Accelerated iTBS for Depression

Major Depressive Disorder Clinical Trial

Official title:

A Randomized Sham-Controlled Trial of High-Dosage Accelerated Intermittent Theta Burst rTMS in Major Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04255784
• Other study ID #: 109-2019
• Status: Recruiting
• Phase: N/A
• Start date: February 6, 2020
• Est. completion date: February 2025

Study information

• Verified date: February 2024
• Source: Centre for Addiction and Mental Health
• Contact: Elizabeth Clancy
• Phone: 416-535-8501
• Email: Elizabeth.Clancy[@]camh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will compare active intermittent theta burst stimulation (iTBS) rTMS in an accelerated treatment schedule (8 treatment sessions per day for 5 days) to a placebo control. Depression symptom severity will be measured before, during, at end of treatment, 1-week post and 4-weeks post treatment.

Description:

Those participants who do not meet the response criterion (50% improvement from baseline on the HRDS-17) at the 4-week follow-up will be offered a second course of treatment, regardless of whether they were in the active or the sham treatment group. The blind will be maintained and no further assessment contributing to the primary or secondary outcomes will occur after the 4-week time point. A different operator will administer the open-label second course of treatment to ensure blinding of operators. The second course of treatment will apply active rTMS using low-frequency (1 Hz) stimulation to the right DLPFC for 600 pulses (10 minutes), 8x daily at 50 minutes (between session and end and start) intervals for 5 days. All those completing the second course of treatment will undergo the same set of clinical assessments during and after the course of treatment on the same schedule as the first course of treatment. The final 4-week follow up assessment from the first course of treatment will serve as the baseline for those that go on to receive the second open label treatment course.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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 65

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

6. have a score > 18 on the HRSD-17 item

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

8. able to adhere to the treatment schedule

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

10. have normal thyroid functioning based on pre-study blood work.

Exclusion Criteria:

1. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis 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, that is 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 subject blinding

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 or a febrile seizure of infancy, 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. clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians

14. currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• Active iTBS
Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30
• Sham iTBS
Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30

Locations

Country	Name	City	State
Canada	CAMH	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	University Health Network, Toronto, University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)	ITT	After 5 treatment days
Secondary	Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)	ITT	one week and four weeks post treatment
Secondary	Proportion of participants achieving response (50% reduction in HRSD-17) and remission (HRSD-17 <8)	ITT	After 5 treatment days and at 1-week and 4 weeks post-treatment
Secondary	Change on the Beck Depression Inventory-II (BDI-II)	ITT	After 5 treatment days and at 1-week and 4 weeks post-treatment
Secondary	Change on the Generalized Anxiety Disorder 7-Item (GAD-7)	ITT	After 5 treatment days and at 1-week and 4 weeks post-treatment