Trial Outcomes & Findings for An Open Label Trial of TMS Therapy for Bipolar Depression (NCT NCT02640950)

Last Updated: 2022-06-01

Results Overview

The MADRS is a clinician rated scale measuring depression severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60; higher scores denote greater severity. A decrease in MADRS score of at lease 50% will be considered a response to treatment. A MADRS score of less than 10 will be considered remission.

Recruitment status

COMPLETED

Study phase

Target enrollment

31 participants

Primary outcome timeframe

Up to 7 weeks

Results posted on

2022-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Patients With Bipolar (I or II) Depression Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015-February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Overall Study STARTED	31
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Patients With Bipolar (I or II) Depression Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015-February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

An Open Label Trial of TMS Therapy for Bipolar Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With Bipolar (I or II) Depression n=31 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015-February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	42.2 years STANDARD_DEVIATION 14.3 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants
Montgomery-Åsberg Depression Rating Scale Participants in remission at baseline	0 Number of participants n=5 Participants
Montgomery-Åsberg Depression Rating Scale Participants responding at baseline	0 Number of participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 weeks

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=31 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
The Percentage of Patients Who Respond or Remit After 30 to 35 Treatments Based Off of the Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Criteria · Number of non-responders	8 Participants
The Percentage of Patients Who Respond or Remit After 30 to 35 Treatments Based Off of the Montgomery-Åsberg Depression Rating Scale (MADRS) Response Criteria · Number meeting criteria	27 Participants
The Percentage of Patients Who Respond or Remit After 30 to 35 Treatments Based Off of the Montgomery-Åsberg Depression Rating Scale (MADRS) Response Criteria · Number of non-responders	4 Participants
The Percentage of Patients Who Respond or Remit After 30 to 35 Treatments Based Off of the Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Criteria · Number meeting criteria	23 Participants

PRIMARY outcome

Timeframe: Up to 7 weeks

The Young Mania Rating Scale (YMRS) is used to determine the severity of a patient's mania. The score for the YMRS ranges form 0 to 60. Scores of 13-19 indicate minimal manic symptoms, 20-25 is mild mania, 26-37 is moderate mania, and 38-60 is severe mania. A YMRS score of 14 or greater will be used for criteria of onset of manic symptoms. The patients will be separated based on their diagnostic category of either Bipolar I Disorder or Bipolar II Disorder.

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=31 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
The Percentage of Patients Who Meet Criteria for Onset of Manic Symptoms Based on the Young Mania Rating Scale (YMRS). Bipolar I Disorder	20 Participants
The Percentage of Patients Who Meet Criteria for Onset of Manic Symptoms Based on the Young Mania Rating Scale (YMRS). Bipolar II Disorder	11 Participants
The Percentage of Patients Who Meet Criteria for Onset of Manic Symptoms Based on the Young Mania Rating Scale (YMRS). Bipolar I Participants with Onset of Maniac Symptoms	0 Participants
The Percentage of Patients Who Meet Criteria for Onset of Manic Symptoms Based on the Young Mania Rating Scale (YMRS). Bipolar II Participants with Onset of Maniac Symptoms	0 Participants

SECONDARY outcome

Timeframe: Up to 7 weeks

The Hamilton Depression (HAM-D) Rating Scale is a scale used to measure one's depression. The scoring from the scale ranges 0 to 53. Higher scores indicate that a person is more depressed. The scoring ranges from 0-7 is normal, 8-13 is mild depression, 14-18 is moderate depression, 19-22 severe depression, and greater than or equal to 23 is very severe depression. The HAM-D response criteria will be based off a HAM-D score drop of at least 50%. Remission HAM-D score will be 7 or less.

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=31 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Hamilton Depression Rating Scale (HAM-D) to Calculate Percentage of Patients Meeting Response Criteria Remission : Met criteria	21 Participants
Hamilton Depression Rating Scale (HAM-D) to Calculate Percentage of Patients Meeting Response Criteria Remission : Non-responders	10 Participants
Hamilton Depression Rating Scale (HAM-D) to Calculate Percentage of Patients Meeting Response Criteria Response : Met criteria	24 Participants
Hamilton Depression Rating Scale (HAM-D) to Calculate Percentage of Patients Meeting Response Criteria Response : Non-responders	7 Participants

SECONDARY outcome

Timeframe: Up to 7 weeks and 6 Month Follow Up

The Clinical Global Impression (CGI) Scale is used to determine the severity of a patient's depression. The scoring for the scale ranges from 1 to 7, where 1 indicates that the patient is normal and 7 indicates a severe depression. Remission criteria for the CGI score will be a 2 or less. Responders and remitters will also be followed for six months after the final treatment to see the durability of response. Percentage of patients' meeting relapse criteria will be calculated.

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=31 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Clinical Global Impression (CGI) to Calculate Percentage of Patients Meeting Response Criteria Remission Criteria During 7 Week Treatment · Met criteria	27 Participants
Clinical Global Impression (CGI) to Calculate Percentage of Patients Meeting Response Criteria Remission Criteria During 7 Week Treatment · Did not meet criteria	4 Participants
Clinical Global Impression (CGI) to Calculate Percentage of Patients Meeting Response Criteria Relapse Criteria During 6 Month Follow Up · Met criteria	9 Participants
Clinical Global Impression (CGI) to Calculate Percentage of Patients Meeting Response Criteria Relapse Criteria During 6 Month Follow Up · Did not meet criteria	22 Participants

SECONDARY outcome

Timeframe: 7 Weeks

For the patients meeting remission criteria (Total Number = 21) , we will calculate the number of treatments required to achieve remission. Patients who only meet response criteria will be treated for 30 to 35 sessions.

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=21 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Hamilton Depression Rating Scale (HAM-D) to Average Number of Treatments Needed to Meet Remission	25.76 Number of Treatments Standard Deviation 5.02

SECONDARY outcome

Timeframe: 7 Weeks

For the patients meeting remission criteria (Total Number = 27) , we will calculate the number of treatments required to achieve remission. Patients who only meet response criteria will be treated for 30 to 35 sessions.

Outcome measures

Outcome measures
Measure	Patients With Bipolar (I or II) Depression n=27 Participants Adults with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015 -February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Clinical Global Impression (CGI) to Calculate Average Number of Treatments Needed to Meet Remission	26.48 Number of Treatments Standard Deviation 4.45

Adverse Events

Patients With Bipolar (I or II) Depression

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Patients With Bipolar (I or II) Depression n=31 participants at risk Thirty-one adults (13M/18F; age: 42.2\[14.3\]) with bipolar (I or II) depression, per DSM-5 criteria, were recruited at Sheppard Pratt and Mayo Clinic between December 2015-February 2020 for TMS. Standardized treatment protocols employed 6 weeks of 10 Hz TMS to the left dorsolateral prefrontal cortex at 120% of motor threshold with 3,000 pulses per session in 4 second trains with intertrain intervals of 26 seconds. All patients were treated concurrently with a mood stabilizer. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). Response and remission were defined as MADRS score reductions of ≥ 50% or score ≤10, respectively. We examined response, remission, and potential contributing factors with multivariate and logistic regression models.
Psychiatric disorders Agitation	3.2% 1/31 • Number of events 1 • Six months

Additional Information

Director of Clinical Research

Sheppard Pratt Health System

Phone: 4109383125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place