Trial Outcomes & Findings for Low Frequency TMS for Depression in Epilepsy (NCT NCT03105700)

Last Updated: 2023-03-21

Results Overview

The hypothesis is that TMS treatment will not produce serious adverse events defined as an increase in the average number of seizures across all participants. This data is collected from the time of enrollment, and then at baseline, 1-week post treatment, 1-month post-treatment, and 6-month post treatment. The seizures are reported directly by the participants during check-ins with the research staff at the study specified study timepoints.

Recruitment status

COMPLETED

Study phase

Target enrollment

15 participants

Primary outcome timeframe

Baseline, 1-week post-treatment, 1-month post-treatment, 6-month post-treatment follow-up

Results posted on

2023-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Low Frequency TMS Intervention Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Overall Study STARTED	15
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Frequency TMS Intervention Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Overall Study screen fail	3
Overall Study Lost to Follow-up	4

Baseline Characteristics

3 prospective participants were screen fails

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Frequency TMS Intervention n=15 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Age, Categorical <=18 years	0 Participants n=12 Participants • 3 prospective participants were screen fails
Age, Categorical Between 18 and 65 years	12 Participants n=12 Participants • 3 prospective participants were screen fails
Age, Categorical >=65 years	0 Participants n=12 Participants • 3 prospective participants were screen fails
Sex: Female, Male Female	8 Participants n=12 Participants • 3 prospective participants were screen fails
Sex: Female, Male Male	4 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) Asian	0 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) Black or African American	0 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) White	12 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) More than one race	0 Participants n=12 Participants • 3 prospective participants were screen fails
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants • 3 prospective participants were screen fails
Region of Enrollment United States	12 participants n=12 Participants • 3 prospective participants were screen fails

PRIMARY outcome

Timeframe: Baseline, 1-week post-treatment, 1-month post-treatment, 6-month post-treatment follow-up

Population: Subjects 3 and14 were lost to 6-month follow-up for unknown reasons. Subjects 9 and 13 were lost to 6-month follow-up due to COVID 19.

Outcome measures

Outcome measures
Measure	Low Frequency TMS Intervention n=12 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Change in Seizure Frequency Expressed as the Average Number of Seizures Experienced by All Participants and Recorded at Specified Time Points Throughout the Study. 1-month post-treatment	1.42 average number of seizures Interval 0.0 to 12.0
Change in Seizure Frequency Expressed as the Average Number of Seizures Experienced by All Participants and Recorded at Specified Time Points Throughout the Study. 6-month post-treatment	1.0 average number of seizures Interval 0.0 to 6.0
Change in Seizure Frequency Expressed as the Average Number of Seizures Experienced by All Participants and Recorded at Specified Time Points Throughout the Study. Baseline	5.83 average number of seizures Interval 0.0 to 40.0
Change in Seizure Frequency Expressed as the Average Number of Seizures Experienced by All Participants and Recorded at Specified Time Points Throughout the Study. 1-week post-treatment	0 average number of seizures Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 15 one-hour sessions of TMS over 3 days

Population: Participants who started the TMS treatment and completed all sessions

The percentage of participants who completed the TMS treatment as measured by the total number of participants (expressed as percentage) who completed 15-hour sessions of TMS over 3 days.

Outcome measures

Outcome measures
Measure	Low Frequency TMS Intervention n=12 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Percentage of Participants Who Complete the TMS Treatment	12 Participants

PRIMARY outcome

Timeframe: Day 1, 2, and 3 of TMS treatment

The hypothesis is that TMS treatment will not be associated with a higher rate of adverse events as measured by a modified Systematic Assessment for Treatment Emergent Events (SAFTEE) given pre-TMS treatment and immediately post-TMS sessions. SAFTEE is a tool used to assess participants' adverse events and is presented to all participants before and right after each TMS session. The outcome is expressed as a total number of adverse events across all participants and all TMS treatment sessions.

Outcome measures

Outcome measures
Measure	Low Frequency TMS Intervention n=12 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Number of Treatment-emergent Adverse Events as Measured by a Modified Systematic Assessment for Treatment Emergent Events (SAFTEE).	1 adverse events

PRIMARY outcome

Timeframe: Baseline, Post-TMS, 1-month and 6-month follow-up

Population: Subject 1: post-TMS HD-EEG data file is not retrievable. Subject 3 and 4: baseline and post-TMS data were too noisy for analysis in frequency domain, and therefore, were excluded from the following analysis. 6-month follow-up: was not collected for this outcome measure due to COVID-19 pandemic

Examine the utility of dense-array electroencephalogram (EEG) as a biological marker (biomarker) of depression and response to treatment with low-frequency transcranial magnetic stimulation (TMS) in patients with Epilepsy. The ratio of alpha power between the right and the left hemispheres is considered an EEG based biomarker for depression. It is obtained by dividing alpha power from the right brain hemisphere divided by alpha power measured from the left brain hemisphere. A ratio higher than 1 (1 infers that both sides of the brain are equal) correlates with depression.

Outcome measures

Outcome measures
Measure	Low Frequency TMS Intervention n=10 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Measuring Biomarker for Depression Using Dense-array EEG Baseline alpha power asymmetry	1.29 frontal alpha power ratio R/L Standard Deviation 0.88
Measuring Biomarker for Depression Using Dense-array EEG Post-TMS alpha power asymmetry	1.10 frontal alpha power ratio R/L Standard Deviation 0.21
Measuring Biomarker for Depression Using Dense-array EEG 1-Month Follow-up alpha power asymmetry	1.35 frontal alpha power ratio R/L Standard Deviation 0.53

SECONDARY outcome

Timeframe: 1-week post-treatment, 1-month post-treatment, 3-month post-treatment, and 6-month post-treatment follow-up

Population: 3-month follow-up: subjects 1 \& 2: data not available as this was not in the protocol at the time 6-month follow-up: subjects 3, 9, 13, 14: lost to follow-up, no data available for analysis

Exploratory analyses will investigate changes in depression scores as a result of the study protocol and interventions. Quick Inventory of Depressive Symptomology (QIDS) is a self-assessment questionnaire used in this study to measure participants' depression symptoms. For Major Depressive Disorder scores of 0-5 indicate no depression, 6-10 indicates mild depression, 11-15 is moderate depression, 16-20 is severe depression, and 21-27 is very severe depression.

Outcome measures

Outcome measures
Measure	Low Frequency TMS Intervention n=12 Participants Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Changes in Depression Severity Related to the Study Interventions. Screening Visit	16.9 score on a scale Interval 9.0 to 21.0
Changes in Depression Severity Related to the Study Interventions. 1-week post treatment	8.2 score on a scale Interval 2.0 to 15.0
Changes in Depression Severity Related to the Study Interventions. 1-month post treatment	8.7 score on a scale Interval 3.0 to 17.0
Changes in Depression Severity Related to the Study Interventions. 3-month post-treatment	8.8 score on a scale Interval 3.0 to 19.0
Changes in Depression Severity Related to the Study Interventions. 6-month post-treatment	9.6 score on a scale Interval 3.0 to 14.0

Adverse Events

Low Frequency TMS Intervention

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Low Frequency TMS Intervention n=12 participants at risk Patients will receive low-frequency TMS on an accelerated schedule over three consecutive days. Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (TMS) is a focal, nonpharmacological, noninvasive method for stimulating the brain and modulating neural network activity. To administer TMS, an electromagnetic coil is placed on the scalp, and uses electrical current to create magnetic fields that depolarize or hyperpolarize neurons in the brain.
Musculoskeletal and connective tissue disorders Lower Back Pain	16.7% 2/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Mild Headache	91.7% 11/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Eye Pain	33.3% 4/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Fatigue	25.0% 3/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
Gastrointestinal disorders Nausea	8.3% 1/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Bilateral Ear Discomfort	8.3% 1/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Blurry Vision	8.3% 1/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.
General disorders Lightheadedness	8.3% 1/12 • The adverse events are collected from each participant beginning at the screening visit up to the 6-month follow up visit. The results are expressed as the total number of adverse events recorded from all participants at the above specific study timeframe.

Additional Information

Krzysztof Bujarski, MD

Dartmouth Hitchcock Medical Center

Phone: 6036505000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place