Trial Outcomes & Findings for Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle (NCT NCT03027414)

Last Updated: 2022-05-17

Results Overview

Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC). Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = \[Zx × 10\] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD \> 2x run SD) were excluded, and "no blink" (peak \< baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.

Recruitment status

COMPLETED

Study phase

Target enrollment

61 participants

Primary outcome timeframe

Pre and post stimulation

Results posted on

2022-05-17

Participant Flow

Participant milestones

Participant milestones
Measure	Substudy 1 Active and Sham HVs that receive active and sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 3 Active and Sham HVs will receive offline TMS to the lest IPS (FPN) Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Overall Study STARTED	28	26
Overall Study COMPLETED	19	20
Overall Study NOT COMPLETED	9	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Substudy 1 Active and Sham n=28 Participants HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 2 Active and Sham HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 3 Active and Sham n=26 Participants HVs will receive offline TMS to the lest IPS (FPN) Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Total n=54 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants	—	26 Participants n=5 Participants	54 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	27.25 years STANDARD_DEVIATION 7.414392375 • n=5 Participants	—	30.46153846 years STANDARD_DEVIATION 8.52701936 • n=5 Participants	28.7962963 years STANDARD_DEVIATION 8.129460894 • n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	—	16 Participants n=5 Participants	31 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	—	10 Participants n=5 Participants	23 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	—	3 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	—	23 Participants n=5 Participants	47 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	—	8 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	—	5 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	—	12 Participants n=5 Participants	28 Participants n=4 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	—	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	28 participants n=5 Participants	—	26 participants n=5 Participants	54 participants n=4 Participants

PRIMARY outcome

Timeframe: Pre and post stimulation

Population: Healthy Volunteers

Outcome measures

Outcome measures
Measure	Substudy 1 Active and Sham n=19 Participants HVs that receive active and sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 3 Active and Sham n=19 Participants HVs will receive offline TMS to the lest IPS (FPN) Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Anxiety-potentiated Startle Active	6.032164105 T-scores Standard Error 1.31706568	2.420193836 T-scores Standard Error 1.174992336
Anxiety-potentiated Startle Sham	3.412441384 T-scores Standard Error 1.02011584	4.467812115 T-scores Standard Error 0.966471881
Anxiety-potentiated Startle No TMS / Pre-stimulation	2.832028871 T-scores Standard Error 0.989278736	4.960918182 T-scores Standard Error 1.111076546

PRIMARY outcome

Timeframe: Pre and post stimulation

Population: No participants were recruited in Substudy 2. Study was stopped because lead investigator (Dr. Balderston) changed position prior to the initiation of Study 2

Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock. Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz. Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = \[Zx × 10\] + 50). Noisy trials (baseline SD \> 2x run SD) are excluded, and "no blink" (peak \< baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).

Outcome measures

Outcome data not reported

Adverse Events

Substudy 1 Active and Sham

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Substudy 2 Active and Sham

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Substudy 3

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Substudy 1 Active and Sham n=28 participants at risk HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 2 Active and Sham HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 3 n=26 participants at risk HVs will receive offline TMS to the lest IPS (FPN) Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Product Issues Possible vasovagal syncope	3.6% 1/28 • Number of events 1 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	— 0/0 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	0.00% 0/26 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.

Other adverse events

Other adverse events
Measure	Substudy 1 Active and Sham n=28 participants at risk HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 2 Active and Sham HVs that receive active and Sham TMS over the right dlPFC Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.	Substudy 3 n=26 participants at risk HVs will receive offline TMS to the lest IPS (FPN) Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Product Issues mild headache	14.3% 4/28 • Number of events 5 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	— 0/0 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	11.5% 3/26 • Number of events 3 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.
Product Issues scalp or face discomfort	10.7% 3/28 • Number of events 3 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	— 0/0 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	0.00% 0/26 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.
Product Issues non-medical device malfunction	3.6% 1/28 • Number of events 1 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	— 0/0 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.	0.00% 0/26 • During study participation, which typically lasted less than 1 month. The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.

Additional Information

Nicholas Balderston

University of Pennsylvania

Phone: 2157463058

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place