Bipolar Efficacy Biomarkers for rTMS

Bipolar Disorder Clinical Trial

Official title:

Bipolar Efficacy Biomarkers for Accelerated Intermittent Theta Burst rTMS Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05393648
• Other study ID #: 800601
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 5, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of repetitive transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression (BPD) who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period. To facilitate the development of rTMS protocols there is a need for biomarkers that are sensitive to BPD symptom severity and clinical improvement. Previously in our lab, investigators developed biomarkers suitable for depression trials, and these biomarkers are very likely to show sensitivity to BPD, since they are associated with brain regions and functions associated with BPD. As a secondary aim, the investigators will try to identify biomarkers in cortical region associated with BPD, and formulate a statistical model that may be able to predict BPD remission after the treatment. this study will lead to development of new brain stimulation treatment protocols and biomarkers, will aid in treatment selection, and eventually lead to better clinical outcome for patients suffering from BPD.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Bipolar depression (BP I and BP II) by DSM 5 criteria (Diagnostic and Statistical Manual of Mental Disorders, 2013)
• Age 18-70
• Right or left handed
• All genders
• Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria (Sackeim et al., 2019)
• Able to provide informed consent to participate in the study
• Must be on a stable medication regimen, requiring at least one mood stabilizer
• Depression severity as represented by scoring at least 20 on MADRS
• Meet the safety criteria as defined in the transcranial magnetic stimulation adult safety screen (TASS).

Exclusion Criteria:

• No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary)
• Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation)
• No dementia or other major neurological disorders
• Not having depression as primary disorder
• No major medical illness, for example metastatic cancer, end stage renal disease
• Not able to verify contact information. Participants must be able to follow through with the study & must have verified contact information and at least one verified contact
• Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary
• Score on YMRS greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment (Tavares et al., 2021).
• Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania (Tondo et al., 2010)
• Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder

Intervention

Device:
• Accelerated Theta Burst Stimulation
Cool B65- A/P - active side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.
• Sham accelerated Theta Burst Stimulation
Cool-B65 A/P - sham side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.

Locations

Country	Name	City	State
United States	UCSD Interventional Psychiatry	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Diego	Milken Institute, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores	Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Montgomery-Asberg Depression Rating Scale (MADRS) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.	6 months
Primary	Change in Hamilton Rating Scale for Depression (HRSD-17) Scores	Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Hamilton Rating Scale for Depression (HRSD-17) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 53, with higher scores indicating more severe depression.	6 months
Primary	Assessment of Biomarkers	Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the left dorsolateral prefrontal cortex (DLPFC) as BPD biomarkers, as measured by scores on the HAMD and MADRS, for aiTBS compared to sham treatment.	6 months