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Intensive TMS for Bipolar Depression

Primary Purpose

Bipolar Depression, Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intensive intermittent theta-burst stimulation (iTBS)
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Bipolar Depression

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Center for Neuromodulation in Depression and Stress, University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active Transcranial Magnetic Stimulation

Sham Transcranial Magnetic Stimulation

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

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 and on each of the five treatment days.

Secondary Outcome Measures

Relationship between change in brain resting state functional connectivity and treatment effects
The main secondary outcome will be the change in correlation of the dorsal lateral prefrontal cortex (DLPFC) with limbic regions, as gathered during baseline and post stimulation MRI scans.

Full Information

First Posted
January 13, 2022
Last Updated
March 6, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT05228457
Brief Title
Intensive TMS for Bipolar Depression
Official Title
Intensive TMS for Rapid Relief of Bipolar Depression Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Depression, Treatment Resistant Depression

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Transcranial Magnetic Stimulation
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Sham Transcranial Magnetic Stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Intensive intermittent theta-burst stimulation (iTBS)
Intervention Description
Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.
Primary Outcome Measure Information:
Title
Clinical efficacy of high dose spaced theta burst (HDS-TBS)
Description
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 and on each of the five treatment days.
Time Frame
Through study completion, approximately 1 week
Secondary Outcome Measure Information:
Title
Relationship between change in brain resting state functional connectivity and treatment effects
Description
The main secondary outcome will be the change in correlation of the dorsal lateral prefrontal cortex (DLPFC) with limbic regions, as gathered during baseline and post stimulation MRI scans.
Time Frame
Upon study completion, approximately 1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvette Sheline, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Neuromodulation in Depression and Stress, University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Walid Makhoul
Phone
215-573-2409
Email
walid.makhoul@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Maria Prociuk
Phone
215-573-4229
Email
lmari@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Yvette Sheline, MD

12. IPD Sharing Statement

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Intensive TMS for Bipolar Depression

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