tDCS-TKA: Dose Dependent Effects of tDCS on Post-Operative Pain

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02241967
• Collaborator: (none)
• Enrollment: 119
• Location: 1
• Arms: 4
• Actual Duration (Months): 53.8
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

The proper control of acute and chronic pain is one of the most important areas in health care. Despite the profound advances in neuroscience over the past 20 years, the investigators still largely use opiate narcotics, much as was done in the Civil War. Total knee arthroplasty (TKA) is one of the most common orthopedic procedures performed 1. While knee pain is often a complaint that precedes TKA, the procedure itself is associated with considerable post-operative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery time and hospital length of stay. New analgesic strategies are needed that can be used adjunctively to existing strategies with the potential to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are beginning to demonstrate promise as treatments for a variety of pain conditions. Electricity has no metabolite or other residue, and can be delivered with minimal discomfort and without problems associated with drug-drug interactions. In two independent preliminary pilot studies, the Investigators have shown that tDCS can reduce post-operative PCA use by as much as 46% while simultaneously reducing subjective pain ratings. The present study aims to determine the effects of transcranial direct current stimulation (tDCS) on post-operative pain, patient-controlled analgesia (PCA) use, and post-surgical complications during the 48-hour post-operative period following total knee arthroplasty.

Condition or Disease	Intervention/Treatment	Phase
Total Knee Arthroplasty (Postoperative Pain); Total Hip Arthroplasty(Postoperative Pain)	Device: 4 Real sessions of Transcranial Direct Current Stimulation; Device: 2 Real Sessions of Transcranial Direct Current Stimulation; Device: 1 Real Session of Transcranial Direct Current Stimulation; Device: Sham Transcranial Direct Current Stimulation	Phase 1

Detailed Description

The proposed study employs a randomized, double-blind, sham-controlled design to evaluate the effects of tDCS on pain among Veterans receiving unilateral total knee arthroplasty (TKA) and unilateral total hip arthroplasty (THA). Further, this study will examine dose-dependency of the tDCS analgesic effects. Each tDCS session delivered either 20 min of real or sham tDCS. Real tDCS was administered at 2mA whereas sham tDCS delivered none.

120 patients undergoing TKA will be randomly assigned to one of four groups:Group 1 will have 4 sessions of real tDCS, Group 2 - 2 sessions of real tDCS (+ 2 sham-sessions), and Group 3 - 1 session of real tDCS (+ 3 sham-sessions). Group 4 is "Sham" tDCS, which does not involve any real stimulation. The participants will receive 2 tDCS treatments on the day of their surgery, and 2 tDCS treatments the day after their surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dose Dependent Effects of tDCS on Post-Operative Pain
• Actual Study Start Date: Jan 7, 2016
• Actual Primary Completion Date: Jul 2, 2020
• Actual Study Completion Date: Jul 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tDCS Full Dose 4 active treatments	Device: 4 Real sessions of Transcranial Direct Current Stimulation; Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp.; Other Names: tDCS Full Dose
Experimental: tDCS Half Dose 2 active treatments	Device: 2 Real Sessions of Transcranial Direct Current Stimulation; Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp. 2 real sessions of tDCS and 2 sham.; Other Names: tDCS Half Dose
Experimental: tDCS Minimal dose 1 active treatment	Device: 1 Real Session of Transcranial Direct Current Stimulation; Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp. 1 real sessions of tDCS and 3 sham.; Other Names: tDCS Minimal Dose
Sham Comparator: Sham tDCS no active treatments	Device: Sham Transcranial Direct Current Stimulation; Four sessions of sham tDCS; control intervention.; Other Names: Sham tDCS

Outcome Measures

Primary Outcome Measures

1. Post-operative Opioid Pain Medication Dose [2-Days]

   Patient Controlled Analgesia pump usage will be measured (mg of morphine-equivalent) during the acute post-operative period.

2. Patient-reported Pain Intensity Ratings [2-Days]

   Patients reported pain intensity using a visual analog scale (VAS) before and after each tDCS session during the 2 day routine postoperative hospital stay. Patients reported pain intensity by marking a line anchored with a minimum of "0- no pain at all" to maximum of "10- worst pain imaginable." Lower values represent a more favorable outcome. This outcome data is the sum of all VAS scores collected before and after each tDCS session during the 2-day hospital stay, thus each participant had a total of 8 VAS scores during the experimental intervention during hospital stay.

Secondary Outcome Measures

1. Patient-reported Average Pain Ratings [6 Months]

   Visual analogue scale pain ratings will be collected during the perioperative and post-discharge periods . Visual analogue scale ratings range from 0-10; a blank line is anchored with a 0 and 10 with the following labels: "0- no pain," "10-worst pain imaginable."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Participants will be 120 patients undergoing TKA or THA surgery at the Ralph H. Johnson VAMC in Charleston SC.

• Between the ages of 19 and 90

• Mentally capable of reading, writing, giving consent, and following instructions

• Cleared for and scheduled for unilateral TKA or THA surgery

Exclusion Criteria:

• Implanted medical devices above the waist

• Pregnant

• History of seizures

• Allergic to latex rubber

• Psychiatric conditions other than for depression and/or anxiety disorders

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ralph H. Johnson VA Medical Center, Charleston, SC	Charleston	South Carolina	United States	29401-5799

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Jeffrey J Borckardt, PhD, Ralph H. Johnson VA Medical Center, Charleston, SC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 8, 2017

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02241967
• Other Study ID Numbers: CLIN-005-13F; CX001078
• First Posted: Sep 16, 2014
• Last Update Posted: Jul 13, 2022
• Last Verified: Jun 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: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: total knee arthroplasty; pain; post-surgical pain; opioid; transcranial direct current stimulation; tDCS; brain stimulation; total hip arthroplasty; TKA; THA
• Additional relevant MeSH terms: Pain, Postoperative

Study Results

Participant Flow

Arm/Group Title	tDCS Full Dose	tDCS Half Dose	tDCS Minimal Dose	Sham tDCS
Arm/Group Description	4 active treatments administered at 2mA for 20minutes each sessions, two the day of surgery and two the day after surgery. Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	2 active treatments administered at 2mA for 20minutes each sessions. 2 real sessions the day of surgery and 2 sham sessions the day after surgery. Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	1 active treatment administered at 2mA for 20minutes for the first session immediately following surgery, then 1 sham session later, day of surgery, and 2 sham sessions the day after surgery. Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	no active treatments. All 4 sessions were sham tDCS. 2 delivered day of surgery, 2 delivered day after surgery. Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.
Period Title: Overall Study
STARTED	30	30	30	29
COMPLETED	30	30	30	29
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	tDCS Full Dose	tDCS Half Dose	tDCS Minimal Dose	Sham tDCS	Total
Arm/Group Description	4 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	2 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	1 active treatment Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	no active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	Total of all reporting groups
Overall Participants	30	30	30	29	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (8.73)	67.0 (8.95)	63.5 (7.93)	64.2 (8.14)	64.7 (8.50)
Sex: Female, Male (Count of Participants)
Female	2 6.7%	1 3.3%	3 10%	1 3.4%	7 5.9%
Male	28 93.3%	29 96.7%	27 90%	28 96.6%	112 94.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	30 100%	29 96.7%	29 96.7%	28 96.6%	116 97.5%
Unknown or Not Reported	0 0%	1 3.3%	1 3.3%	1 3.4%	3 2.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	8 26.7%	7 23.3%	10 33.3%	9 31%	34 28.6%
White	22 73.3%	22 73.3%	19 63.3%	19 65.5%	82 68.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.3%	1 3.3%	1 3.4%	3 2.5%
Region of Enrollment (Count of Participants)
United States	30 100%	30 100%	30 100%	29 100%	119 100%
Procedure Type (Count of Participants)
Total Knee Arthroplasty (TKA)	18 60%	21 70%	23 76.7%	20 69%	82 68.9%
Total Hip Arthroplasty (THA)	12 40%	9 30%	7 23.3%	9 31%	37 31.1%

Outcome Measures

1. Primary Outcome

Title	Post-operative Opioid Pain Medication Dose
Description	Patient Controlled Analgesia pump usage will be measured (mg of morphine-equivalent) during the acute post-operative period.
Time Frame	2-Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tDCS Full Dose	tDCS Half Dose	tDCS Minimal Dose	Sham tDCS
Arm/Group Description	4 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	2 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	1 active treatment Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	no active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.
Measure Participants	30	30	30	29
Mean (Standard Error) [mg of morphine equivalent dose (MED)]	26.99 (2.99)	31.12 (3.73)	28.65 (31.12)	33.15 (5.60)

2. Primary Outcome

Title	Patient-reported Pain Intensity Ratings
Description	Patients reported pain intensity using a visual analog scale (VAS) before and after each tDCS session during the 2 day routine postoperative hospital stay. Patients reported pain intensity by marking a line anchored with a minimum of "0- no pain at all" to maximum of "10- worst pain imaginable." Lower values represent a more favorable outcome. This outcome data is the sum of all VAS scores collected before and after each tDCS session during the 2-day hospital stay, thus each participant had a total of 8 VAS scores during the experimental intervention during hospital stay.
Time Frame	2-Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tDCS Full Dose	tDCS Half Dose	tDCS Minimal Dose	Sham tDCS
Arm/Group Description	4 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	2 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	1 active treatment Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.	no active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.
Measure Participants	29	28	29	27
Mean (Standard Error) [score on a scale]	5.33 (.44)	5.59 (.43)	5.84 (.48)	5.33 (.56)

3. Secondary Outcome

Title	Patient-reported Average Pain Ratings
Description	Visual analogue scale pain ratings will be collected during the perioperative and post-discharge periods . Visual analogue scale ratings range from 0-10; a blank line is anchored with a 0 and 10 with the following labels: "0- no pain," "10-worst pain imaginable."
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	tDCS Full Dose	tDCS Half Dose	tDCS Minimal Dose	Sham tDCS
Arm/Group Description	4 active treatments 4 Real sessions of Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp.	2 active treatments 2 Real Sessions of Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp. 2 real sessions of tDCS and 2 sham.	1 active treatment 1 Real Session of Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current of 2mA delivered by electrodes attached to the scalp. 1 real sessions of tDCS and 3 sham.	no active treatments Sham Transcranial Direct Current Stimulation: Four sessions of sham tDCS; control intervention.
Measure Participants	16	11	13	9
Mean (Standard Error) [score on a scale]	3.06 (.46)	3.45 (.72)	3.77 (.74)	4.89 (.59)

Adverse Events

Time Frame	2-Days during the routine post-operative hospital stay; the duration in which tDCS was delivered.
Arm/Group Title	tDCS Full Dose		tDCS Half Dose		tDCS Minimal Dose		Sham tDCS
Arm/Group Description	4 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.		2 active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.		1 active treatment Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.		no active treatments Transcranial Direct Current Stimulation: Stimulation of brain areas associated with pain perception using low amplitude direct current delivered by electrodes attached to the scalp.
All Cause Mortality
	tDCS Full Dose		tDCS Half Dose		tDCS Minimal Dose		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)		0/29 (0%)
Serious Adverse Events
	tDCS Full Dose		tDCS Half Dose		tDCS Minimal Dose		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	tDCS Full Dose		tDCS Half Dose		tDCS Minimal Dose		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)		0/29 (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.