Modulating Impulsivity in Suicidal Adolescents With Transcranial Direct Current Stimulation (tDCS)

• Sponsor: Lifespan (Other)
• Overall Status: Completed
• CT.gov ID: NCT03365102
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 3
• Actual Duration (Months): 33
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

As a first step toward investigating whether modulation of impulsivity and associated neural pathways may yield clinically meaningful changes in risk for adolescent suicidal behavior, the R21 is a proof-of concept study evaluating the potential for tDCS targeting brain regions associated with behavioral impulsivity (right inferior frontal gyrus [rIFG]) and cognitive impulsivity (left orbitofrontal cortex [lOFC]) to modulate these facets of impulsivity in a sample of adolescent suicide attempters. Participants will be randomly assigned to receive anodal tDCS over the rIFG, anodal tDCS over the lOFC, or a sham stimulation condition, in a three-group design. Task-based measures of behavioral and cognitive impulsivity will be administered before and after tDCS or sham stimulation. Additionally, electroencephalography (EEG) and event-related potential (ERP) data will be collected during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS administration to confirm engagement of the targeted brain regions and to delineating the neural pathways underlying the effects of tDCS on impulsivity.

Condition or Disease	Intervention/Treatment	Phase
Impulsive Behavior	Device: anodal tDCS over the rIFG,; Device: anodal tDCS over the lOFC,; Device: sham tDCS stimulation condition	N/A

Detailed Description

Suicide is one of the leading causes of death in adolescence. To improve the ability to predict and prevent suicidal behavior, there is a pressing need for research in this area to advance beyond identifying risk factors toward a greater focus on the mechanisms of risk for this behavior. In particular, elucidating the neural pathways underlying risk for suicidal behavior is important insofar as such work may yield specific and modifiable targets for clinical intervention. The adoption of new experimental paradigms providing experimental control over potentially modifiable risk factors has been recommended as a means of meaningfully advancing the field in this regard. Although yet to be applied to the study of suicidality, transcranial direct current stimulation (tDCS), in conjunction with measures of electroencephalography (EEG) and event-related potentials (ERPs), may hold promise as an experimental paradigm in the study of potentially modifiable risk factors, and underlying neural mechanisms, for suicidality. One such risk factor of particular relevance to suicide in adolescence is state-sensitive aspects of impulsivity. Impulsivity has been consistently linked with suicidality, with this association appearing to be stronger in adolescence than adulthood. As a first step toward investigating whether modulation of impulsivity and associated neural pathways may yield clinically meaningful changes in risk for adolescent suicidal behavior, the R21 is a proof-of concept study evaluating the potential for tDCS targeting brain regions associated with behavioral impulsivity (right inferior frontal gyrus [rIFG]) and cognitive impulsivity (left orbitofrontal cortex [lOFC]) to modulate these facets of impulsivity in a sample of adolescent suicide attempters. Participants will be randomly assigned to receive anodal tDCS over the rIFG, anodal tDCS over the lOFC, or a sham stimulation condition, in a three-group design. Task-based measures of behavioral and cognitive impulsivity will be administered before and after tDCS or sham stimulation. Additionally, EEG and ERP data will be collected during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS administration to confirm engagement of the targeted brain regions and to delineating the neural pathways underlying the effects of tDCS on impulsivity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: anodal tDCS over the rIFG, anodal tDCS over the lOFC, sham stimulation conditionanodal tDCS over the rIFG, anodal tDCS over the lOFC, sham stimulation condition
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Neither participant or outcome aware of condition
• Primary Purpose: Diagnostic
• Official Title: Modulating Impulsivity in Suicidal Adolescents With tDCS: A Proof of Concept Study
• Actual Study Start Date: Apr 1, 2017
• Actual Primary Completion Date: Dec 31, 2019
• Actual Study Completion Date: Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anodal tDCS over the rIFG, anodal tDCS over the rIFG,	Device: anodal tDCS over the rIFG,; tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Experimental: anodal tDCS over the lOFC anodal tDCS over the lOFC	Device: anodal tDCS over the lOFC,; tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Placebo Comparator: sham tDCS stimulation sham tDCS stimulation	Device: sham tDCS stimulation condition; In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.

Outcome Measures

Primary Outcome Measures

1. Stop Signal Task (SST) [Within an hour post-stimulation condition]

   The Stop-Signal Task (SST) is a task requiring inhibition of a prepotent motor response. The SST requires participants to respond to a target stimulus as quickly and accurately as possible by pressing a button, but also to withhold their response when they hear an auditory signal. Thus, this task involves a competition between activating and inhibiting processes. The primary outcome variable is change in the stop signal reaction time (SSRT) for the task administered seconds to minutes before and seconds to minutes after stimulation. The theoretical minimum is zero seconds and there is no theoretical maximum. Higher SSRT scores reflect greater impulsivity.

2. Delay Discounting Task [Within an hour post-stimulation condition]

   This task assessed discounting larger future rewards for smaller immediate ones. The point where a person is equally likely to prefer immediate vs delayed reward (the indifference point) is determined for several and combinations of reward sizes and lengths of time. Area under the curve (AUC) is calculated by summing the results of the following for each delay and indifference point pair: x2-x1[(y1 + y2)/2]. x1 and x2 are successive delays and y1 and y2 are indifference points for those delays. AUC range=0-1. Larger AUCs reflect less impulsivity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• have attempted suicide prior to admission

• speak and read English fluently

• do not display evidence of significant cognitive impairment, based on a standard psychiatric exam as well as school records on admission

• are not actively psychotic at time of intake.

Exclusion Criteria:

• a significant general medical condition

• history of seizure, head injury, brain surgery or tumor

• intracranial metallic implants or implanted electrical devices

• substance abuse or dependence in the past six months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bradley Hospital	Riverside	Rhode Island	United States	02915

Sponsors and Collaborators

• Lifespan

Investigators

• Principal Investigator: Richard Liu, PhD, Lifespan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 16, 2019

More Information

Publications

None provided.

• Responsible Party: Richard Liu, Assistant Professor, Lifespan
• ClinicalTrials.gov Identifier: NCT03365102
• Other Study ID Numbers: Liu 002017
• First Posted: Dec 7, 2017
• Last Update Posted: Feb 2, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Impulsive Behavior

Study Results

Participant Flow

Arm/Group Title	Anodal tDCS Over the rIFG,	Anodal tDCS Over the lOFC	Sham tDCS Stimulation
Arm/Group Description	anodal tDCS over the rIFG, anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	anodal tDCS over the lOFC anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	sham tDCS stimulation sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Period Title: Overall Study
STARTED	22	22	20
COMPLETED	18	21	19
NOT COMPLETED	4	1	1

Baseline Characteristics

Arm/Group Title	Anodal tDCS Over the rIFG,	Anodal tDCS Over the lOFC	Sham tDCS Stimulation	Total
Arm/Group Description	anodal tDCS over the rIFG, anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	anodal tDCS over the lOFC anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	sham tDCS stimulation sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	Total of all reporting groups
Overall Participants	18	21	19	58
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	21 100%	19 100%	58 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	14 77.8%	17 81%	14 73.7%	45 77.6%
Male	4 22.2%	4 19%	5 26.3%	13 22.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 27.8%	5 23.8%	2 10.5%	12 20.7%
Not Hispanic or Latino	13 72.2%	16 76.2%	17 89.5%	46 79.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 5.3%	1 1.7%
Asian	1 5.6%	0 0%	0 0%	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 16.7%	2 9.5%	3 15.8%	8 13.8%
White	7 38.9%	12 57.1%	12 63.2%	31 53.4%
More than one race	7 38.9%	6 28.6%	3 15.8%	16 27.6%
Unknown or Not Reported	0 0%	1 4.8%	0 0%	1 1.7%
Region of Enrollment (participants) [Number]
United States	18 100%	21 100%	19 100%	58 100%
PROMIS Depression (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	49 (10)	47 (12)	47 (12)	47.64285714 (11.22728587)
Conners-3 Self-Report (units on a scale) [Mean (Standard Deviation) ]
Inattention subscale	16 (8)	16 (9)	15 (8)	15.67857143 (8.250855918)
Hyperactivity/impulsivity subscale	14 (7)	17 (7)	12 (7)	14.39285714 (7.191354839)
Stop Signal Task (milliseconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliseconds]	353 (414)	276 (328)	233 (247)	284.8076923 (330.2148165)
Delay discounting task (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	.45 (.3)	.31 (.22)	.5 (.31)	0.415454545 (0.284301081)

Outcome Measures

1. Primary Outcome

Title	Stop Signal Task (SST)
Description	The Stop-Signal Task (SST) is a task requiring inhibition of a prepotent motor response. The SST requires participants to respond to a target stimulus as quickly and accurately as possible by pressing a button, but also to withhold their response when they hear an auditory signal. Thus, this task involves a competition between activating and inhibiting processes. The primary outcome variable is change in the stop signal reaction time (SSRT) for the task administered seconds to minutes before and seconds to minutes after stimulation. The theoretical minimum is zero seconds and there is no theoretical maximum. Higher SSRT scores reflect greater impulsivity.
Time Frame	Within an hour post-stimulation condition

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anodal tDCS Over the rIFG,	Anodal tDCS Over the lOFC	Sham tDCS Stimulation
Arm/Group Description	anodal tDCS over the rIFG, anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	anodal tDCS over the lOFC anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	sham tDCS stimulation sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Measure Participants	15	15	17
Mean (Standard Deviation) [milliseconds]	255 (463)	215 (278)	297 (278)

2. Primary Outcome

Title	Delay Discounting Task
Description	This task assessed discounting larger future rewards for smaller immediate ones. The point where a person is equally likely to prefer immediate vs delayed reward (the indifference point) is determined for several and combinations of reward sizes and lengths of time. Area under the curve (AUC) is calculated by summing the results of the following for each delay and indifference point pair: x2-x1[(y1 + y2)/2]. x1 and x2 are successive delays and y1 and y2 are indifference points for those delays. AUC range=0-1. Larger AUCs reflect less impulsivity.
Time Frame	Within an hour post-stimulation condition

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anodal tDCS Over the rIFG,	Anodal tDCS Over the lOFC	Sham tDCS Stimulation
Arm/Group Description	anodal tDCS over the rIFG, anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	anodal tDCS over the lOFC anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.	sham tDCS stimulation sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Measure Participants	17	18	18
Mean (Standard Deviation) [score on a scale]	.53 (.31)	.4 (.25)	.57 (.29)

Adverse Events

Time Frame	1 hour
Arm/Group Title	Anodal tDCS Over the rIFG,		Anodal tDCS Over the lOFC		Sham tDCS Stimulation
Arm/Group Description	anodal tDCS over the rIFG, anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.		anodal tDCS over the lOFC anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.		sham tDCS stimulation sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
All Cause Mortality
	Anodal tDCS Over the rIFG,		Anodal tDCS Over the lOFC		Sham tDCS Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)		0/20 (0%)
Serious Adverse Events
	Anodal tDCS Over the rIFG,		Anodal tDCS Over the lOFC		Sham tDCS Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Anodal tDCS Over the rIFG,		Anodal tDCS Over the lOFC		Sham tDCS Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)		0/20 (0%)

Limitations/Caveats

Multiple and persistent technical problems were experienced with the device used in this study. It was not possible to confirm that stimulation reliably occurred and that therefore all study participants received then intended stimulation. Caution should therefore be taken in interpreting the results of this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.