Transcranial Magnetic Stimulation for Attention Deficit/Hyperactivity Disorder (ADHD)

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT03663179
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 36
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study will test the effects of transcranial magnetic stimulation (TMS) on clinical measures of ADHD symptoms.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Disorder With Hyperactivity (ADHD)	Device: Transcranial Magnetic Stimulation (TMS); Device: Sham Transcranial Magnetic Stimulation (Sham TMS)	N/A

Detailed Description

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by symptoms of impulsivity, inattention, and hyperactivity that emerge in childhood and frequently persist into adulthood. These symptoms are accompanied by deficits in cognitive control and risky decision making that can lead to negative psychosocial and health-related outcomes. With advances in the neuroimaging field, researchers are learning where and how self-control over decisions and behaviors is executed in the brain. This work points to the central role of neural activity in the dorsolateral prefrontal cortices (DLPFC) in self-control processes that contribute to healthy choices. Emerging evidence shows that activity in the prefrontal cortices and cognitive control circuits can be modulated using a noninvasive and safe intervention: repetitive TMS. This within-subject proof of concept study will investigate whether 20 sessions of TMS (versus sham stimulation) can enhance executive cognitive function in adults with ADHD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Repetitive Transcranial Magnetic Stimulation for Adult ADHD
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Mar 31, 2019
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active TMS Participants will receive 20 sessions of active TMS targeting the left DLPFC.	Device: Transcranial Magnetic Stimulation (TMS); A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).
Sham Comparator: Sham TMS Participants will receive 20 sessions of sham TMS over the left DLPFC.	Device: Sham Transcranial Magnetic Stimulation (Sham TMS); A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).

Outcome Measures

Primary Outcome Measures

1. Change in Performance on Conners Adult ADHD Rating Scale - Self-Report: Long Version (ADHD Symptoms) [Baseline and week 4]

   ADHD symptoms will be assessed using the well-validated Conners Adult ADHD Rating Scale - Self-Report: Long Version (CAARS-S:L). The CAARS-S:L is a 66-item rating scale designed to assess ADHD symptoms in adults. The scale contains multiple subscales to assess Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) specified ADHD criteria as well as other facets of ADHD such as inattention/memory problems, hyperactivity/restlessness, impulsivity/emotionality, and problems with self-concept. Subscale results are converted to T-scores (range: 25-90), where 50 is the standardized population mean and every 10 points indicates one standard deviation from the mean. Higher values generally indicate more difficulties with ADHD symptoms. This measure will be administered at baseline at at the end of 4 weeks of treatment. The primary outcome will be the change from baseline to week 4.

Secondary Outcome Measures

1. Change in Performance on Conners Continuous Performance Task (Sustained Attention) [Baseline and week 4]

   The Conners Continuous Performance Task (Conners CPT) will be administered and baseline and weekly during the treatment period to assess sustained attention. In this task, participants are shown a series of letters on a computer screen and are asked to press the spacebar in response to all letters except for the letter X. The primary outcome for the Conners CPT is the change in number of commission errors (e.g., false positives) from baseline to week 4.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Eligible participants will be:

1. Healthy males and females who are between 18 and 65 years of age with an ADHD diagnosis (meet diagnostic criteria for ADHD on the SCID-5 module for adult ADHD).

2. Planning to live in the area for at least the next 6 weeks;

3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form;

4. Able to communicate fluently in English (speaking, writing, and reading).

Exclusion Criteria:

Subjects who present and/or self-report with the following criteria at any point during study participation will not be eligible to participate in the study:

Alcohol/Drugs:

1. History or current diagnosis or treatment for alcohol or drug abuse (as reported during phone screen);

2. Positive breath alcohol concentration test (BrAC greater than or equal to 0.01) at intake;

3. A positive urine drug screen for cocaine, phencyclidine (PCP), amphetamines, methamphetamines, benzodiazepines, methadone, and/or barbiturates at Intake, Baseline, or Sessions 5, 10, 15 or 20.

Medication:

Current use or recent discontinuation (within the past 6 months at the time of Intake) of:

1. Gamma-Aminobutyric Acid (GABA)-ergic medications

2. Glutamatergic medications

3. Any medication for the treatment of ADHD

4. Benzodiazepines

5. Any medication that is known to lower the seizure threshold (e.g.,clozapine, bupropion, tramadol, carbapenems, stimulants)

6. Any medication that could compromise participant safety as determined by the Principal Investigator and/or Study Physician

Current use or recent discontinuation (within the last 14 days at the time of Intake) of:

1. Anti-psychotic medications

2. Nicotine replacement therapy (NRT)

Daily use of:

1. Opiate-containing medications for chronic pain

Medical/Neuropsychiatric:

1. Women who are pregnant, planning a pregnancy, and/or breast feeding.

2. History of seizures, epilepsy, or history of epilepsy in first-degree relative

3. History of stroke or transient ischemic attack (warning stroke)

4. History of traumatic brain injury or self-report of brain or spinal tumor

5. History of head injury with unconsciousness lasting more than 5 minutes

6. Previous brain surgery

7. Any additional neurological condition that would likely reduce the safety of study participation, including central nervous system (CNS) vasculitis, intracranial tumor, intracranial aneurysm, multiple sclerosis or arteriovenous malformations

8. History of tinnitus

9. History of diabetes mellitus

10. History of atherosclerotic vascular disease

11. A medically unstable cardiopulmonary or metabolic disorder

12. Increased risk for myocardial infarction or other major cardiopulmonary complications.

13. Any uncorrected visual impairment or abnormality

14. Self-reported history, current diagnosis of psychosis or symptoms consistent with a mood disorder based upon the Structured Clinical Interview for DSM-5 (SCID); including schizophrenia, mania, bipolar disorder, an eating disorder, obsessive compulsive disorder, an anxiety disorder, major depression (subjects with a history of major depression but in remission for past 6 months are eligible).

TMS-related:

1. Subjects with ferromagnetic material in or in close proximity to the head (with the exception of oral dental devices)

2. Implanted devices (including vagus nerve stimulator (VNS), deep brain stimulator (DBS), pacemakers, spinal cord stimulators, medication pumps, ventriculo peritoneal shunts, defibrillators, intracardiac lines)

3. Self-report of any skull fracture or opening

4. A disturbance in normal sleep patterns/sleep deprivation

General Exclusion:

1. Any medical condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, or affect clinical or cognitive outcomes, as determined by the Principal Investigator

2. Inability to complete study tasks and provide quality data, as determined by the Principal Investigator

3. Low or borderline intellectual functioning - determined by a score of less than 90 on the Shipley Institute of Living Scale (SILS) (administered at Intake Visit). The SILS correlates with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated Intelligence Quotient (IQ) Test

4. Inability to provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: James Loughead, PhD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 29, 2019

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT03663179
• Other Study ID Numbers: 826586
• First Posted: Sep 10, 2018
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by University of Pennsylvania: ADHD; TMS
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity

Study Results

Participant Flow

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	Participants will receive 20 sessions of active TMS targeting the left DLPFC. Transcranial Magnetic Stimulation (TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).	Participants will receive 20 sessions of sham TMS over the left DLPFC. Sham Transcranial Magnetic Stimulation (Sham TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).
Period Title: Overall Study
STARTED	18	14
COMPLETED	14	13
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Active TMS	Sham TMS	Total
Arm/Group Description	Participants will receive 20 sessions of active TMS targeting the left DLPFC. Transcranial Magnetic Stimulation (TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).	Participants will receive 20 sessions of sham TMS over the left DLPFC. Sham Transcranial Magnetic Stimulation (Sham TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).	Total of all reporting groups
Overall Participants	14	13	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.9 (9.9)	36.0 (6.0)	34.4 (13.0)
Sex: Female, Male (Count of Participants)
Female	5 35.7%	4 30.8%	9 33.3%
Male	9 64.3%	9 69.2%	18 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 7.1%	1 7.7%	2 7.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 14.3%	2 15.4%	4 14.8%
White	10 71.4%	9 69.2%	19 70.4%
More than one race	1 7.1%	1 7.7%	2 7.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Education (Count of Participants)
high school/some college	7 50%	4 30.8%	11 40.7%
college graduate	7 50%	9 69.2%	16 59.3%
Smoking Status (Count of Participants)
smokers	4 28.6%	2 15.4%	6 22.2%
non-smokers	10 71.4%	11 84.6%	21 77.8%

Outcome Measures

1. Primary Outcome

Title	Change in Performance on Conners Adult ADHD Rating Scale - Self-Report: Long Version (ADHD Symptoms)
Description	ADHD symptoms will be assessed using the well-validated Conners Adult ADHD Rating Scale - Self-Report: Long Version (CAARS-S:L). The CAARS-S:L is a 66-item rating scale designed to assess ADHD symptoms in adults. The scale contains multiple subscales to assess Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) specified ADHD criteria as well as other facets of ADHD such as inattention/memory problems, hyperactivity/restlessness, impulsivity/emotionality, and problems with self-concept. Subscale results are converted to T-scores (range: 25-90), where 50 is the standardized population mean and every 10 points indicates one standard deviation from the mean. Higher values generally indicate more difficulties with ADHD symptoms. This measure will be administered at baseline at at the end of 4 weeks of treatment. The primary outcome will be the change from baseline to week 4.
Time Frame	Baseline and week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	Participants will receive 20 sessions of active TMS targeting the left DLPFC. Transcranial Magnetic Stimulation (TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).	Participants will receive 20 sessions of sham TMS over the left DLPFC. Sham Transcranial Magnetic Stimulation (Sham TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).
Measure Participants	14	13
Mean (Standard Deviation) [t-score]	-4.4 (9.4)	-5.1 (7.6)

2. Secondary Outcome

Title	Change in Performance on Conners Continuous Performance Task (Sustained Attention)
Description	The Conners Continuous Performance Task (Conners CPT) will be administered and baseline and weekly during the treatment period to assess sustained attention. In this task, participants are shown a series of letters on a computer screen and are asked to press the spacebar in response to all letters except for the letter X. The primary outcome for the Conners CPT is the change in number of commission errors (e.g., false positives) from baseline to week 4.
Time Frame	Baseline and week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active TMS	Sham TMS
Arm/Group Description	Participants will receive 20 sessions of active TMS targeting the left DLPFC. Transcranial Magnetic Stimulation (TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).	Participants will receive 20 sessions of sham TMS over the left DLPFC. Sham Transcranial Magnetic Stimulation (Sham TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).
Measure Participants	14	13
Mean (Standard Deviation) [Commission Errors]	-16.2 (17.6)	-4.8 (18.0)

Adverse Events

Time Frame	Baseline until end of treatment, an average of 4 weeks.
Arm/Group Title	Active TMS		Sham TMS
Arm/Group Description	Participants will receive 20 sessions of active TMS targeting the left DLPFC. Transcranial Magnetic Stimulation (TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. TMS will be administered at 10 Hertz (Hz) with an intensity of 120% of patient resting motor threshold. Stimulation will be delivered to the left dorsolateral prefrontal cortex using 20 sec cycles (i.e., 5 sec train with 15 sec inter train interval). Subjects will receive 80 trains per session for a total of 4000 pulses per session (~26 min sessions). Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).		Participants will receive 20 sessions of sham TMS over the left DLPFC. Sham Transcranial Magnetic Stimulation (Sham TMS): A MagPro R30 (Magventure, Inc., Copenhagen, Denmark) device with a Cool-B65 A/P figure 8 coil will be used to deliver TMS. This coil has an active side and a sham side, and can be used to perform double-blinded studies. For sham stimulation, the sham side of the coil is positioned toward the participant's scalp. The sham coil is designed to mimic the appearance and sound of active TMS stimulation, but is equipped with a magnetic shield that reduces the strength of the field by approximately 80%. This reduction in field strength ensures that no neural stimulation occurs. Twenty sessions will be completed on sequential weekdays (5 days per week for 4 weeks).
All Cause Mortality
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/14 (0%)
Serious Adverse Events
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Active TMS		Sham TMS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)		1/14 (7.1%)
Eye disorders
Visual disturbance	0/18 (0%)	0	1/14 (7.1%)	1
General disorders
Sleep disturbance	1/18 (5.6%)	1	0/14 (0%)	0
Immune system disorders
allergic reaction	1/18 (5.6%)	1	0/14 (0%)	0
Injury, poisoning and procedural complications
Injury	1/18 (5.6%)	1	0/14 (0%)	0
Psychiatric disorders
Depression symptoms	1/18 (5.6%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.