Theta-Burst Stimulation for Bipolar Depression

Bipolar Disorder Clinical Trial

— TRIBE  

Official title:

Theta-Burst Stimulation for Bipolar Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06370988
• Other study ID #: 4343
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: May 2029

Study information

• Verified date: April 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

The purpose of this trial is to determine if intermittent theta-burst stimulation (iTBS) can reduce the symptoms of depression in treatment-resistant bipolar disorder. To do this, some of the participants in this study will receive treatment with active iTBS stimulation, while others will receive sham iTBS stimulation. Participants will come for 30 days of either active iTBS or sham iTBS, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 124
• Est. completion date: May 2029
• Est. primary completion date: May 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

The participant must meet all of the inclusion criteria to eligible for this clinical

trial:

1. Must be deemed to have capacity to provide informed consent;

2. Must be an outpatient;

3. Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI);

4. Age 18-65;

5. failure to achieve a clinical response to =1 adequate treatment trial for bipolar depression based on the Antidepressant Treatment History Form - Short Form (ATHF-SF) OR unable to tolerate at least 2 separate inadequate treatment trials;

6. moderately severe depression with a score = 15 on the PHQ-9;

7. not currently experiencing a mixed or manic episode (YMRS =10);

8. no increase or initiation of psychotropic medication with intention of treating depressive symptoms in the 4 weeks prior to screening. This excludes targeted treatment of insomnia with trazodone, melatonin, low-dose doxepin [3-6mg], low-dose benzodiazepines [=2mg lorazepam daily equivalent], non-benzodiazepine benzodiazepine receptor agonists, or orexin antagonists;

9. currently receiving treatment with one of the following non-anticonvulsant mood stabilizer with evidence for prevention of mania: lithium, quetiapine, asenapine, aripiprazole, paliperidone (>6mg), risperidone, olanzapine, ziprasidone, haloperidol, clozapine (lurasidone and cariprazine are excluded due to lack of evidence for preventing mania);

10. able to adhere to the treatment schedule;

11. pass the TMS adult safety screening questionnaire. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation

in this clinical trial:

1. have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months;

2. have a concomitant major unstable medical illness;

3. have active suicidal intent (assessed during HRSD-17 Item 3 and SSRS as imminent intent to act on specific plan, confirmed by psychiatric staff);

4. are pregnant or intend to get pregnant during the study;

5. have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;

6. have psychotic symptoms within the current episode;

7. have a MINI anxiety disorder, trauma-related disorder, obsessive compulsive disorder, or personality disorder assessed by a study investigator to be primary and/or causing greater impairment than BD-DE;

8. failure of an adequate acute course of ECT as defined by ATHF-SF during the current episode;

9. have received any rTMS before due to potential to compromise blinding of treatment allocation;

10. have any clinically significant neurological disorder (e.g., recent major cerebrovascular accident), or any history of seizure except those therapeutically induced by ECT or with clear precipitant (e.g., febrile seizure of childhood, alcohol withdrawal, etc.);

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

12. are participating in psychotherapy for less than 3 months. Patients will be permitted if they have been in stable treatment for at least 3 months prior to study entry, with no anticipated change in the frequency of therapeutic sessions, or focus of therapeutic sessions over the duration of the study;

13. are currently taking lorazepam >2 mg daily (or equivalent) due to the potential to limit rTMS efficacy;

14. are currently taking any dose of an anticonvulsant due to the potential to limit rTMS efficacy. If anticonvulsants have been discontinued prior to screening, at least 5 half-lives have elapsed until screening to allow sufficient drug clearance;

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

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder
• Treatment- Resistant Bipolar Disorder

Intervention

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

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (2)

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

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)	Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17), ITT, 6 weeks (completion of treatment phase (30 txs)). The main effect of interest is the interaction term between time since starting treatment and treatment allocation. This analytic approach incorporates longitudinal depressive symptom assessments throughout the trial rather solely at treatment completion.	From enrollment to 6 weeks post-treatment
Secondary	Symptoms of Mania	Safety of rTMS in BD-DE with respect to symptoms of mania, Young Mania Rating Scale (YMRS), Safety Outcomes, 6 weeks (completion of treatment phase (30 txs)). The main effect of interest is the interaction term between time since starting treatment and treatment allocation. This analytic approach incorporates longitudinal depressive symptom assessments throughout the trial rather solely at treatment completion.	From enrollment to 6 weeks post-treatment