TES: The Safety and Efficacy of Nexalin Trans-cranial Electrical Stimulation Stimulation for the Treatment of Depression

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT03277846
• Collaborator: Carrier Clinic (Other)
• Enrollment: 101
• Location: 1
• Arms: 4
• Actual Duration (Months): 8.5
• Patients Per Site Per Month: 11.9

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine whether Nexalin Trans-Cranial Electrical Stimulation (TES) is an effective treatment for depression among patients who are candidates for ECT. A secondary aim to assess whether Nexalin can be used as an alternative to ECT. Although Nexalin has been approved for use in the US, using Nexalin to treat depression in this way is investigational and experimental. If Nexalin is found to be an alternative to ECT, it could offer a safer treatment for depression with less side-effects and a lower cost.

!!! NOTE !!! Post Script / Post Study. The ECT arm (profiling subjects as ECT accepters vs. rejecters) was dropped owing to site objections by referring clinicians. Accordingly, the study was framed as a simple comparison between TES and SHAM TES.

Condition or Disease	Intervention/Treatment	Phase
Depression	Device: Nexalin Based Trans-Cranial Electrical Stimulation	N/A

Detailed Description

A 2x2 factor Randomized Controlled Trial with block randomization. Inpatient subjects at the Carrier Clinic who are referred for ECT will be recruited, typed regarding their acceptance of ECT, and randomized to either treatment with TES or to a Sham condition. Treatment non-responders in either condition will continue as in patients at the Carrier Clinic until they reach acceptable levels of functioning to be discharged.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A 2x2 factor Randomized Controlled Trial with block randomizationA 2x2 factor Randomized Controlled Trial with block randomization
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: All participants and investigators are blind to condition.
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of Nexalin Electrical Brain Stimulation for the Treatment of Depression in Patients Referred to Electro-Convulsive Therapy
• Actual Study Start Date: Sep 1, 2017
• Actual Primary Completion Date: May 17, 2018
• Actual Study Completion Date: May 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Accept ECT - TES Accept ECT where subject is randomized to TES	Device: Nexalin Based Trans-Cranial Electrical Stimulation; The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a square waveform that provides trans-cranial electrical stimulation to the brain delivered at a frequency of 77.5 Hz at 0 to 4 mA peak current.; Other Names: TES
Placebo Comparator: Accept ECT - SHAM Accept ECT where subject is randomized to a SHAM condition	Device: Nexalin Based Trans-Cranial Electrical Stimulation; The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a square waveform that provides trans-cranial electrical stimulation to the brain delivered at a frequency of 77.5 Hz at 0 to 4 mA peak current.; Other Names: TES
Experimental: Reject ECT - TES Reject ECT where subject is randomized to TES	Device: Nexalin Based Trans-Cranial Electrical Stimulation; The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a square waveform that provides trans-cranial electrical stimulation to the brain delivered at a frequency of 77.5 Hz at 0 to 4 mA peak current.; Other Names: TES
Placebo Comparator: Reject ECT - SHAM Reject ECT where subject is randomized to SHAM	Device: Nexalin Based Trans-Cranial Electrical Stimulation; The Nexalin device, FDA clearance (501K=K024377, Classification: Stimulator, Cranial Electrotherapy: CFR 882. 5800: U.S. Patent #6904322B2), produces a square waveform that provides trans-cranial electrical stimulation to the brain delivered at a frequency of 77.5 Hz at 0 to 4 mA peak current.; Other Names: TES

Outcome Measures

Primary Outcome Measures

1. Treatment Response [1-2 weeks]

   Percent responders to TES treatment and Sham TES (50% reduction or a score below 10 on the PHQ-9). The PHQ-9 is a 9 item scale, where each item ranges from 0 to 3. Zero represents "not at all" and 3 represents "nearly every day". The scale ranges from 0-27. We used percent change (from admission to "ex-take") as a our metric.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. In-patients at the Carrier Clinic

2. Adults over age 18 and under age 65

3. Able to speak, read and write fluently in English, assessed by the study coordinator at Carrier Clinic

4. Screened Negative for alcohol abuse and/or dependence

5. Able to provide informed consent, assessed by the study coordinator at Carrier Clinic

6. Referred for ECT

7. Not currently taking hypnotics or be prescribed hypnotics during the Nexalin trial

8. Not pregnant or intending to become pregnant during the study

9. Committed to completion of the study

Exclusion Criteria: Medically or psychiatrically unstable, where the severity of the illness prohibits the subject from engaging in study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carrier Clinic	Belle Mead	New Jersey	United States	08502

Sponsors and Collaborators

• University of Pennsylvania
• Carrier Clinic

Investigators

• Principal Investigator: Michael L Perlis, PhD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 10, 2017

More Information

Publications

• Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19. Review.
• Bestmann S, Walsh V. Transcranial electrical stimulation. Curr Biol. 2017 Dec 4;27(23):R1258-R1262. doi: 10.1016/j.cub.2017.11.001.
• Yavari F, Jamil A, Mosayebi Samani M, Vidor LP, Nitsche MA. Basic and functional effects of transcranial Electrical Stimulation (tES)-An introduction. Neurosci Biobehav Rev. 2018 Feb;85:81-92. doi: 10.1016/j.neubiorev.2017.06.015. Epub 2017 Jul 6. Review.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT03277846
• Other Study ID Numbers: IRB 824349
• First Posted: Sep 11, 2017
• Last Update Posted: Oct 28, 2019
• Last Verified: Oct 1, 2019

• 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: Depression; Depressive Disorder

Study Results

Participant Flow

Arm/Group Title	Transcranial Electrical Stimulation (Active)	TES SHAM
Arm/Group Description	All subjects get active treatment with Transcranial Electrical Stimulation	All subjects get SHAM treatment with TES
Period Title: Overall Study
STARTED	50	51
COMPLETED	38	40
NOT COMPLETED	12	11

Baseline Characteristics

Arm/Group Title	Transcranial Electrical Stimulation	SHAM -TES	Total
Arm/Group Description	Transcranial Electrical Stimulation (TES). Active Treatment.	Sham/placebo condition	Total of all reporting groups
Overall Participants	50	51	101
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	50 100%	51 100%	101 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.6 (2.4)	35.9 (2.3)	34.2 (2.35)
Sex: Female, Male (Count of Participants)
Female	20 40%	20 39.2%	40 39.6%
Male	30 60%	31 60.8%	61 60.4%
Race/Ethnicity, Customized (Count of Participants)
White	35 70%	32 62.7%	67 66.3%
African American	3 6%	0 0%	3 3%
Asian	0 0%	1 2%	1 1%
Native American	0 0%	1 2%	1 1%
Multi-Racial	0 0%	2 3.9%	2 2%
Hispanic	4 8%	5 9.8%	9 8.9%
Unknown	8 16%	10 19.6%	18 17.8%
Region of Enrollment (participants) [Number]
United States	50 100%	51 100%	101 100%

Outcome Measures

1. Primary Outcome

Title	Treatment Response
Description	Percent responders to TES treatment and Sham TES (50% reduction or a score below 10 on the PHQ-9). The PHQ-9 is a 9 item scale, where each item ranges from 0 to 3. Zero represents "not at all" and 3 represents "nearly every day". The scale ranges from 0-27. We used percent change (from admission to "ex-take") as a our metric.
Time Frame	1-2 weeks

Outcome Measure Data

Analysis Population Description

101 were enrolled. 78 subjects were in study for the minimum time / minimum number of treatments and provided the full compliment of data.

Arm/Group Title	Transcranial Electrical Stimulation	TES-SHAM
Arm/Group Description	Transcranial Electrical Stimulation (Active Tx)	SHAM treatment (no current). Otherwise procedures identical.
Measure Participants	38	40
Count of Participants [Participants]	28 56%	29 56.9%

Adverse Events

Time Frame	1 year
Arm/Group Title	Transcranial Electrical Stimulation		SHAM-TES
Arm/Group Description	TES = Transcranial Electrical Stimulation (active treatment)		TES. No current. Procedures were otherwise identical between conditions
All Cause Mortality
	Transcranial Electrical Stimulation		SHAM-TES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Serious Adverse Events
	Transcranial Electrical Stimulation		SHAM-TES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Transcranial Electrical Stimulation		SHAM-TES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)

Limitations/Caveats

[Not Specified]

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.