Intensive TMS for Bipolar Depression

NCT ID: NCT05228457

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2024-02-19

Brief Summary

The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of 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 who have failed (or not shown signs of improvement) after at least two prior treatments.

Detailed Description

The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of 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 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. Participants will be randomly assigned to active or sham conditions: 50% to active and 50% to sham.

Conditions

Bipolar Depression; Treatment Resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Active Transcranial Magnetic Stimulation

Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC).

Group Type: ACTIVE_COMPARATOR

Intensive intermittent theta-burst stimulation (iTBS)

Intervention Type: DEVICE

Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.

Sham Transcranial Magnetic Stimulation

Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation.

Group Type: SHAM_COMPARATOR

Intensive intermittent theta-burst stimulation (iTBS)

Intervention Type: DEVICE

Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.

Interventions

Intensive intermittent theta-burst stimulation (iTBS)

Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Bipolar depression (BP I and BP II) by Diagnostic and Statistical Manual 5 (DSM 5) criteria
• 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
• 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 Montgomery-Asberg Depression Rating Scale (MADRS)

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 Young Mania Rating Scale (YMRS) greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment)
• 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)
• Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI
• Currently using benzodiazepines (such as lorazepam) with a dose >1 mg per day or equivalent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Yvette Sheline

McLure Professor of Radiology, Neurology and Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yvette Sheline, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Center for Neuromodulation in Depression and Stress, University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Sheline YI, Makhoul W, Batzdorf AS, Nitchie FJ, Lynch KG, Cash R, Balderston NL. Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Sep 1;81(9):936-941. doi: 10.1001/jamapsychiatry.2024.1787.

Reference Type: DERIVED

PMID: 38985492 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

850359

Identifier Type: -

Identifier Source: org_study_id