Intensive TMS for Bipolar Depression

NCT05228457 | Completed Results FDA Device

• 1 other identifier: 850359
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Depression; Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS)

  The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline, on each of the five treatment days and post TMS.

  Through study completion, approximately 1 week

Secondary Outcomes (1)

• Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects

  Upon study completion, approximately 1 week

Study Arms (2)

Active Transcranial Magnetic Stimulation

ACTIVE COMPARATOR

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).

Device: Intensive intermittent theta-burst stimulation (iTBS)

Sham Transcranial Magnetic Stimulation

SHAM COMPARATOR

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.

Device: Intensive intermittent theta-burst stimulation (iTBS)

Interventions

Intensive intermittent theta-burst stimulation (iTBS) DEVICE

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

Active Transcranial Magnetic Stimulation; Sham Transcranial Magnetic Stimulation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Center for Neuromodulation in Depression and Stress, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 38985492 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder

Results Point of Contact

• Title: Walid Makhoul
• Organization: University of Pennsylvania

walid.makhoul@pennmedicine.upenn.edu

215-573-2409

Study Officials

• Yvette Sheline, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: McLure Professor of Radiology, Neurology and Psychiatry

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: February 8, 2022
• Study Start: March 1, 2022
• Primary Completion: February 19, 2024
• Study Completion: February 19, 2024
• Last Updated: March 12, 2025
• Results First Posted: March 12, 2025

Record last verified: 2025-02

Locations

US (1)