Effects of tDCS and tUS on Pain Perception in OA of the Knee

• Sponsor: Spaulding Rehabilitation Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02723929
• Collaborator: Highland Instruments, Inc. (Industry)
• Enrollment: 64
• Location: 1
• Arms: 2
• Duration (Months): 70.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effects of transcranial direct current stimulation (tDCS) in conjunction with transcranial ultrasound (TUS) on pain perception and functional limitations in people with osteoarthritis of the knee. The investigators hypothesize that there will be a decrease in pain levels with active stimulation, when compared to sham stimulation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain; Osteoarthritis	Device: active low-intensity transcranial electrical stimulation/active transcranial ultrasound; Device: Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: tDCS and tUStDCS and tUS
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Transcranial Direct Current Stimulation (tDCS) and Transcranial Ultrasound (TUS) on the Perception of Pain and Functional Limitations Due to Osteoarthritis of the Knee
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Aug 15, 2019
• Anticipated Study Completion Date: Jul 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Electrical Stim/Active Ultrasound Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes.	Device: active low-intensity transcranial electrical stimulation/active transcranial ultrasound; Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.
Sham Comparator: Sham Electrical Stim/Sham Ultrasound Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes.	Device: Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound; Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.

Outcome Measures

Primary Outcome Measures

1. Changes in Pain Scale as Measured by VAS [Baseline and 8 weeks]

   Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain and is reported following the full course of therapy. Since we are using a difference, smaller values (negative) represent a better outcome

Secondary Outcome Measures

1. Average Daily Dose of Acetaminophen Equivalent [8 weeks]

   Analgesic use (average daily dose of acetaminophen equivalent)

2. Changes in Pain Scale as Measured by VAS [Baseline and 4 weeks post-stimulation]

   Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain. Since we are using a difference, smaller values (negative) represent a better outcome.

3. Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline [Baseline and 8 weeks]

   This measures the endogenous pain modulatory pathway. This study will evaluate DNIC in pain patients using pressure as the test stimulus, and cold water as the conditioning stimulus. DNIC will be induced approximately 1-min later by having subjects immerse their hand into a water bath maintained at 10-12˚C for approximately 1 min. Parallel to the last 30s of DNIC conditioning (cold water immersion), the pressure test stimulus will be reapplied. DNIC response will be calculated as the difference between the average of pain ratings from the test stimulus minus the average of pain ratings during the conditioned stimulus. Larger percentage change means a better outcome.

4. Percentage Change From Baseline in the Single Leg Standing Balance Test [Baseline and 8 weeks]

   We will record the time (seconds) for which a subject is able to stand unsupported on one foot while looking straight ahead with hands on hips. Larger percentage change means a better outcome.

5. Percentage Change From Baseline in the Step Test [Baseline and 8 weeks]

   The subject was asked to stand unsupported with their feet parallel to each other in front of a step. We assessed the number of times the participant could place their foot up onto the step and return it to the floor over a 15-sec interval. Larger percentage change means a better outcome.

6. Percentage Change in Functional Reach Test From Baseline [Baseline and 8 weeks]

   Subject will be instructed to stand next to, but not touch the wall, and position the arm that is closer to the wall at 90 degrees of shoulder flexion with a closed fist. Smoothness of wrist movement is assessed as the subject was asked to outstretch their arm in a maximal forward reach, while maintaining a fixed base of support. Smoothness is dimensionless and is calculated as mean speed divided by peak speed. Larger percentage change means a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Able to provide informed consent to participate in the study.

2. Subjects between 18-85 years old.

3. Diagnosis of chronic osteoarthritis with pain of either knee as self-reported.

4. Existing knee pain of at least 3 on a 0-10 VAS scale on average over the past 6 months.

5. Pain of at least 3 on a 0-10 VAS scale on average over the week prior to the first stimulation session.

6. Pain resistant to common analgesics and medications for chronic pain used as initial pain management such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, and Codeine.

7. Having the ability to feel pain as self-reported.

Exclusion Criteria:

1. Pregnancy or trying to become pregnant in the next 6 months.

2. History of alcohol or drug abuse within the past 6 months as self-reported

3. Contraindications to transcranial brain stimulation or TUS, i.e. implanted brain medical devices or implanted brain metallic devices.

4. Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease).

5. Epilepsy.

6. Use of carbamazepine within the past 6 months as self-reported.

7. Suffering from severe depression (with a score of >30 in the Beck Depression Inventory)

8. History of unexplained fainting spells as self-reported.

9. Head injury resulting in more than a momentary loss of consciousness

10. History of neurosurgery as self-reported.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spaulding Rehabilitation Network Research Institute	Charlestown	Massachusetts	United States	02129

Sponsors and Collaborators

• Spaulding Rehabilitation Hospital
• Highland Instruments, Inc.

Investigators

None specified.

Study Documents (Full-Text)

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

More Information

Publications

None provided.

• Responsible Party: Felipe Fregni, MD, PhD, MPH, Principal Investigator, Spaulding Rehabilitation Hospital
• ClinicalTrials.gov Identifier: NCT02723929
• Other Study ID Numbers: 2016P000486
• First Posted: Mar 31, 2016
• Last Update Posted: Aug 17, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Felipe Fregni, MD, PhD, MPH, Principal Investigator, Spaulding Rehabilitation Hospital: transcranial direct current stimulation; transcranial ultrasound; non-invasive brain stimulation
• Additional relevant MeSH terms: Osteoarthritis; Chronic Pain

Study Results

Participant Flow

Pre-assignment Detail	64 subjects were enrolled and randomized

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. Active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Period Title: Overall Study
STARTED	30	34
COMPLETED	24	24
NOT COMPLETED	6	10

Baseline Characteristics

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound	Total
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.	Total of all reporting groups
Overall Participants	30	34	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (8.4)	61.8 (8.7)	61.6 (8.5)
Sex: Female, Male (Count of Participants)
Female	16 53.3%	18 52.9%	34 53.1%
Male	14 46.7%	16 47.1%	30 46.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.3%	2 5.9%	3 4.7%
Not Hispanic or Latino	25 83.3%	26 76.5%	51 79.7%
Unknown or Not Reported	4 13.3%	6 17.6%	10 15.6%
Region of Enrollment (Count of Participants)
United States	30 100%	34 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Pain Scale as Measured by VAS
Description	Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain and is reported following the full course of therapy. Since we are using a difference, smaller values (negative) represent a better outcome
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. Active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [units on a scale]	-2.21 (0.2)	-1.6 (0.1)

2. Secondary Outcome

Title	Average Daily Dose of Acetaminophen Equivalent
Description	Analgesic use (average daily dose of acetaminophen equivalent)
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [Acetaminophen equivalent in mg]	390.7 (47.1)	1116.4 (98.6)

3. Secondary Outcome

Title	Changes in Pain Scale as Measured by VAS
Description	Changes in the Visual Analogue Scale (VAS) for pain were measured in order to determine whether transcranial direct current stimulation in conjunction with transcranial ultrasound is effective in reducing pain in subjects with Osteoarthritis of the Knee. The VAS scale goes from 0 up to 10, where 0 means no pain at all and 10 means the worst imaginable pain. Since we are using a difference, smaller values (negative) represent a better outcome.
Time Frame	Baseline and 4 weeks post-stimulation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [units on a scale]	-2.91 (0.38)	-1.28 (0.30)

4. Secondary Outcome

Title	Percentage Change in Diffuse Noxious Inhibitory Controls (DNIC) From Baseline
Description	This measures the endogenous pain modulatory pathway. This study will evaluate DNIC in pain patients using pressure as the test stimulus, and cold water as the conditioning stimulus. DNIC will be induced approximately 1-min later by having subjects immerse their hand into a water bath maintained at 10-12˚C for approximately 1 min. Parallel to the last 30s of DNIC conditioning (cold water immersion), the pressure test stimulus will be reapplied. DNIC response will be calculated as the difference between the average of pain ratings from the test stimulus minus the average of pain ratings during the conditioned stimulus. Larger percentage change means a better outcome.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [Percentage change from baseline]	12 (2.9)	4.0 (1.8)

5. Secondary Outcome

Title	Percentage Change From Baseline in the Single Leg Standing Balance Test
Description	We will record the time (seconds) for which a subject is able to stand unsupported on one foot while looking straight ahead with hands on hips. Larger percentage change means a better outcome.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [Percentage change from baseline]	17.5 (4.5)	3.0 (3.1)

6. Secondary Outcome

Title	Percentage Change From Baseline in the Step Test
Description	The subject was asked to stand unsupported with their feet parallel to each other in front of a step. We assessed the number of times the participant could place their foot up onto the step and return it to the floor over a 15-sec interval. Larger percentage change means a better outcome.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [Percentage change from baseline]	27.0 (2.0)	18.7 (1.8)

7. Secondary Outcome

Title	Percentage Change in Functional Reach Test From Baseline
Description	Subject will be instructed to stand next to, but not touch the wall, and position the arm that is closer to the wall at 90 degrees of shoulder flexion with a closed fist. Smoothness of wrist movement is assessed as the subject was asked to outstretch their arm in a maximal forward reach, while maintaining a fixed base of support. Smoothness is dimensionless and is calculated as mean speed divided by peak speed. Larger percentage change means a better outcome.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Electrical Stim/Active Ultrasound	Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.	Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
Measure Participants	30	34
Mean (Standard Error) [Percentage change from baseline]	12.4 (2.8)	3.3 (2.3)

Adverse Events

Time Frame	2 months
Adverse Event Reporting Description	Adverse effects were collected with a questionnaire for adverse effects
Arm/Group Title	Active Electrical Stim/Active Ultrasound		Sham Electrical Stim/Sham Ultrasound
Arm/Group Description	Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. active low-intensity transcranial electrical stimulation/active transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation. During active stimulation, the current will be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for the full 20 minutes.		Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. Sham low-intensity transcranial electrical stimulation/sham transcranial ultrasound: Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation, as in the active condition; however, during sham stimulation (placebo) the current will not be active for the full 20 minutes. Subjects will also undergo 20 minutes of transcranial ultrasound in the same par. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.
All Cause Mortality
	Active Electrical Stim/Active Ultrasound		Sham Electrical Stim/Sham Ultrasound
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/34 (0%)
Serious Adverse Events
	Active Electrical Stim/Active Ultrasound		Sham Electrical Stim/Sham Ultrasound
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Active Electrical Stim/Active Ultrasound		Sham Electrical Stim/Sham Ultrasound
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)		29/34 (85.3%)
Nervous system disorders
Tingling	23/30 (76.7%)		29/34 (85.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.