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Theta Burst Stimulation in Young Adults With Depression

Theta Burst Stimulation in Young Adults With Depression

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03737032
Enrollment
29
Registered
2018-11-09
Start date
2020-01-31
Completion date
2022-07-31
Last updated
2024-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression

Brief summary

For the proposed 2-year study, the investigators will conduct a within-subject, counterbalanced investigation using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to examine the acute effects of theta-burst stimulation (TBS) on function in dorsomedial prefrontal cortex (dmPFC) in 35 young adults with depression (18-25 years, 50% female).

Detailed description

Each participant will undergo 3 sessions of TMS, one each of continuous and intermittent TBS--with the goal of decreasing or increasing dmPFC responding, respectively--and one of sham TBS. Session order will be counterbalanced, with a double-blind approach to condition. Brain function, behavior, and mood will be assessed before and after each TBS session. Broadly, the investigators predict that inhibitory TBS to the dmPFC will enhance neural, behavioral, and subjective aspects of reward function by reducing dmPFC function and dmPFC connectivity with the ventral striatum (VS).

Interventions

DEVICEIntermittent Theta Burst Stimulation

Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds.

Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds.

For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation. Sham TBS will be delivered with a Cool-B65 Active/Placebo Coil, which includes a sham setting, and MagLink research software.

Sponsors

National Institute of Mental Health (NIMH)
CollaboratorNIH
Erika Forbes
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)

Masking description

The content of each TBS condition will be unknown to participants and to the research staff member conducting assessment of change neural, behavioral, and subjective response with TBS.

Intervention model description

All participants will receive intermittent Theta Burst Stimulation (TBS), continuous TBS, and sham TBS mimicking stimulation, in randomized, double-blind order across three sessions.

Eligibility

Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No

Inclusion criteria

• DSM-5 Diagnosis of Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Other Specified Depressive Disorder, or Other Unspecified Depressive Disorder

Exclusion criteria

* Bipolar disorder, substance dependence, or lifetime history of psychosis * Neurological disorder (e.g., seizure disorder) * Pregnant * MRI contradictions: claustrophobia, permanent orthodontic devices, metal implants or other forms of metal in the body that cannot be removed

Design outcomes

Primary

MeasureTime frameDescription
Dorsomedial Prefrontal Cortex ActivationTask fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order) at approx 3, 5, and 7 weeks after study entry.This measure captures brain function in the dorsomedial prefrontal cortex (dmPFC) based on blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) during a reward task. Data are analyzed using Statistical Parametric Mapping. Magnitude of dmPFC response is in arbitrary units, with higher values reflecting higher activation. Theoretical minimum and maximum scores do not exist. Study hypotheses predict that dmPFC will decrease (based on statistical significance) with continuous TBS.

Secondary

MeasureTime frameDescription
Positive Affectpre and post each of 3 TBS administrations, with TBS lasting up to 190 seconds. cTBS, iTBS, and sham TBS each occurred in a single day.Self-reported pleasant mood was measured with the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS). This scale consists of a number of words that describe different feelings and emotions, participants are instructed to read each item and then mark to which extent they have felt like this in the past few hours. The PA scale contains 10 items, with each item rated on a 5-point scale of 1 (very slightly or not at all), 2 (a little), 3 (moderately), 4 (quite a bit), or 5 (extremely). Higher scores indicate greater PA. The total PA score is calculated by finding the sum of the 10 positive items. Scores range from 10-50. A higher score indicates higher intensity of positive affect. The PANAS PA data analyzed were from administrations pre- and post-TBS at visits #3-5 (approximately 30 minutes before and 1 hour after TBS administration).
VS-dmPFC Functional ConnectivityTask fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order). Sessions occur at approx 3, 5, and 7 weeks after study entry.Outcome measure is assessed with functional magnetic resonance imaging (fMRI), in which brain function is recorded during a reward task. Functional connectivity between 2 regions of neural reward circuitry, the ventral striatum (VS) and the dorsomedial prefrontal cortex (dmPFC), is computed using general psychophysiologic interaction for this pair of regions in Statistical Parametric Mapping software. FC data are in arbitrary units, with higher values reflecting higher degree of coordination between the regions. Theoretical minimum and maximum scores do not exist. Higher scores do not represent better or worse outcomes or change in health. Based on study hypotheses, FC is predicted to decrease with continuous TBS, based on significance of statistical tests.

Countries

United States

Participant flow

Pre-assignment details

29 participants completed enrollment in the study. Prior to randomization, all 29 participants completed study visit #1 and study visit #2. Out of those 29, 4 participants were withdrawn after study visit #2 and before randomization. 25 participants were randomized and completed the study intervention.

Participants by arm

ArmCount
Intermittent, Continuous, Sham Order
3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Continuous theta burst stimulation, 3) Sham theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
5
Intermittent, Sham, Continuous Order
3 sessions of theta burst stimulation administered in the following order: 1) Intermittent theta burst stimulation, 2) Sham theta burst stimulation, 3) Continuous theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
4
Continuous, Intermittent, Sham Order
3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Sham theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
4
Continuous, Sham, Intermittent Order
3 sessions of theta burst stimulation administered in the following order: 1) Continuous theta burst stimulation, 2) Sham theta burst stimulation, 3) Intermittent theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
5
Sham, Intermittent, Continuous Order
3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Intermittent theta burst stimulation, 3) Continuous theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
4
Sham, Continuous, Intermittent Order
3 sessions of theta burst stimulation administered in the following order: 1) Sham theta burst stimulation, 2) Continuous theta burst stimulation, 3) Intermittent theta burst stimulation. Intermittent Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered without interruption for a total duration of 40 seconds. Continuous Theta Burst Stimulation: Theta Burst Stimulation, a form of Transcranial Magnetic Stimulation, will be applied to the dorsomedial prefrontal cortex. will include 600 pulses delivered in brief bursts of three pulses with a frequency of 50 Hz, at an intensity of 110% of resting motor threshold, and administered every 200 ms (5 Hz). Bursts will be delivered during 2 second periods (10 bursts/period) interleaved with 8-second stimulation-free intervals, for a total duration of 190 seconds. Sham Theta Burst Stimulation: For the sham of theta burst stimulation, the device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
3
Total25

Baseline characteristics

CharacteristicIntermittent, Continuous, Sham OrderTotalSham, Continuous, Intermittent OrderSham, Intermittent, Continuous OrderContinuous, Sham, Intermittent OrderContinuous, Intermittent, Sham OrderIntermittent, Sham, Continuous Order
Age, Continuous21 years
STANDARD_DEVIATION 1.22
21.175 years
STANDARD_DEVIATION 2.15
21 years
STANDARD_DEVIATION 1.73
20.25 years
STANDARD_DEVIATION 2.63
21.8 years
STANDARD_DEVIATION 2.39
22 years
STANDARD_DEVIATION 2.45
21 years
STANDARD_DEVIATION 2.45
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants22 Participants3 Participants4 Participants5 Participants3 Participants3 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants2 Participants0 Participants0 Participants0 Participants1 Participants1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants6 Participants1 Participants1 Participants1 Participants0 Participants2 Participants
Race (NIH/OMB)
Black or African American
2 Participants3 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
2 Participants16 Participants2 Participants3 Participants4 Participants3 Participants2 Participants
Region of Enrollment
United States
5 participants25 participants3 participants4 participants5 participants4 participants4 participants
Sex: Female, Male
Female
5 Participants23 Participants3 Participants4 Participants5 Participants2 Participants4 Participants
Sex: Female, Male
Male
0 Participants2 Participants0 Participants0 Participants0 Participants2 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 250 / 250 / 25
other
Total, other adverse events
0 / 250 / 251 / 25
serious
Total, serious adverse events
0 / 250 / 250 / 25

Outcome results

Primary

Dorsomedial Prefrontal Cortex Activation

This measure captures brain function in the dorsomedial prefrontal cortex (dmPFC) based on blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) during a reward task. Data are analyzed using Statistical Parametric Mapping. Magnitude of dmPFC response is in arbitrary units, with higher values reflecting higher activation. Theoretical minimum and maximum scores do not exist. Study hypotheses predict that dmPFC will decrease (based on statistical significance) with continuous TBS.

Time frame: Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order) at approx 3, 5, and 7 weeks after study entry.

Population: Cases included in analysis are those from participants who completed all study procedures (i.e., all TMS sessions, all MRI scans), had available data, and passed data quality criteria

ArmMeasureValue (MEAN)Dispersion
Intermittent TBSDorsomedial Prefrontal Cortex Activation0.16 score in arbitrary unitsStandard Deviation 3.79
Continuous TBSDorsomedial Prefrontal Cortex Activation1.35 score in arbitrary unitsStandard Deviation 4.3
Sham TBSDorsomedial Prefrontal Cortex Activation0.36 score in arbitrary unitsStandard Deviation 3.6
Comparison: Null hypothesis: post-TBS dmPFC activation will not vary by TBS condition. This is tested using the main effect of condition in a repeated measures model.p-value: 0.8ANOVA
Secondary

Positive Affect

Self-reported pleasant mood was measured with the Positive Affect (PA) scale of the Positive and Negative Affect Schedule (PANAS). This scale consists of a number of words that describe different feelings and emotions, participants are instructed to read each item and then mark to which extent they have felt like this in the past few hours. The PA scale contains 10 items, with each item rated on a 5-point scale of 1 (very slightly or not at all), 2 (a little), 3 (moderately), 4 (quite a bit), or 5 (extremely). Higher scores indicate greater PA. The total PA score is calculated by finding the sum of the 10 positive items. Scores range from 10-50. A higher score indicates higher intensity of positive affect. The PANAS PA data analyzed were from administrations pre- and post-TBS at visits #3-5 (approximately 30 minutes before and 1 hour after TBS administration).

Time frame: pre and post each of 3 TBS administrations, with TBS lasting up to 190 seconds. cTBS, iTBS, and sham TBS each occurred in a single day.

Population: Only participants who completed the PA measure at all time points (pre/post each condition, all 3 conditions) were included in analyses.

ArmMeasureGroupValue (MEAN)Dispersion
Intermittent TBSPositive AffectPre20.70 score on a scaleStandard Deviation 6.74
Intermittent TBSPositive AffectPost20.45 score on a scaleStandard Deviation 7.35
Continuous TBSPositive AffectPre20.05 score on a scaleStandard Deviation 6.24
Continuous TBSPositive AffectPost19.80 score on a scaleStandard Deviation 7.8
Sham TBSPositive AffectPost22.10 score on a scaleStandard Deviation 9.71
Sham TBSPositive AffectPre20.45 score on a scaleStandard Deviation 6.06
Comparison: Null hypothesis: pre-post change in positive affect will not vary by TBS condition. This is tested using the interaction of time\*condition in a repeated measures model.p-value: 0.23ANOVA
Secondary

VS-dmPFC Functional Connectivity

Outcome measure is assessed with functional magnetic resonance imaging (fMRI), in which brain function is recorded during a reward task. Functional connectivity between 2 regions of neural reward circuitry, the ventral striatum (VS) and the dorsomedial prefrontal cortex (dmPFC), is computed using general psychophysiologic interaction for this pair of regions in Statistical Parametric Mapping software. FC data are in arbitrary units, with higher values reflecting higher degree of coordination between the regions. Theoretical minimum and maximum scores do not exist. Higher scores do not represent better or worse outcomes or change in health. Based on study hypotheses, FC is predicted to decrease with continuous TBS, based on significance of statistical tests.

Time frame: Task fMRI is conducted after each of 3 TBS sessions (intermittent, continuous, sham; in randomized, counterbalanced order). Sessions occur at approx 3, 5, and 7 weeks after study entry.

Population: Cases included in analysis are those from participants who completed all MRI scans, had available fMRI data, and had data that passed quality criteria

ArmMeasureValue (MEAN)Dispersion
Intermittent TBSVS-dmPFC Functional Connectivity2.28 arbitrary unitsStandard Deviation 7.64
Continuous TBSVS-dmPFC Functional Connectivity4.10 arbitrary unitsStandard Deviation 13.7
Sham TBSVS-dmPFC Functional Connectivity1.16 arbitrary unitsStandard Deviation 5.61
Comparison: Null hypothesis: post-TBS functional connectivity between the dmPFC and ventral striatum (VS) will not vary by TBS condition. This is tested using the main effect of condition in a repeated measures model.p-value: 0.84ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026