Pulsed Electromagnetic Fields for Postoperative Analgesia: A Randomized, Triple-Masked, Sham-Controlled Pilot Study

Study Overview
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Brief Summary
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Pulsed electromagnetic field therapy is a possible method of pain control involving the application of electromagnetic energy (also termed nonthermal, pulsed, shortwave radiofrequency therapy). Food and Drug Administration-cleared devices have been in clinical use for over 70 years. For decades, available devices consisted of a large signal generator and bulky coil applicator that were not portable and produced significant electromagnetic interference, making them impractical for common use. However, small, lightweight, relatively inexpensive, noninvasive, Food and Drug Administration-cleared devices that function for 30 days are now available to treat acute and chronic pain, decrease inflammation and edema, and hasten wound healing and bone regeneration. Therefore, it has the potential to concurrently improve analgesia and decrease or even negate opioid requirements, only without the limitations of opioids and peripheral nerve blocks. The purpose of this pilot study is to explore the possibility of treating acute postoperative pain with nonthermal, pulsed shortwave (radiofrequency) therapy, optimize the study protocol, and estimate the treatment effect in preparation for developing subsequent definitive clinical trials.

Detailed Description
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The proposed study will be a randomized, participant- and observer-masked, sham-controlled, parallel-arm, human participants pilot study with two primary aims: Specific Aim 1: To determine the feasibility and optimize the protocol for subsequent clinical trials that will compare the addition of nonthermal, pulsed shortwave therapy to usual and customary analgesia following moderate-to-severely painful surgical procedures. Specific Aim 2: To estimate the treatment effect of adding nonthermal, pulsed shortwave therapy to usual and customary analgesia on pain and opioid consumption following moderate-to-severely painful surgical procedures. This will provide an idea of the optimal surgical procedures amenable to this analgesic technique and allow determination of the required sample sizes of subsequent definitive clinical trials. Hypothesis 1: Nonthermal, pulsed shortwave therapy decreases pain in the 7 days following moderate-to-severely painful surgical procedures. Hypothesis 2: Nonthermal, pulsed shortwave therapy decreases opioid use in the 7 days following moderate-to-severely painful surgical procedures. This will be a single-center (University of California San Diego), randomized, participant- and observer-masked, sham-controlled, parallel-arm human subjects pilot study. Enrollment. Participants will be consenting adults undergoing various surgical procedures usually resulting in moderate-to-severe postoperative pain. Study inclusion will be proposed to eligible presurgical patients. If an individual desires study participation, written, informed consent will be obtained using a current University of California San Diego Institutional Review Board-approved informed consent form. The study population of interest includes adult women and men of all races, ethnicity, sexual identity, and socioeconomic status. Procedures. Following written, informed consent, we will record baseline anthropometric information (age, sex, height, weight, amputation details and current pain levels). Participants will receive any standard peripheral nerve block(s) administered using bupivacaine or ropivacaine 0.5% with epinephrine (standard at University of California San Diego) prior to undergoing their surgical procedure per standard of care. Treatment Group Assignment. Each participant will be randomized to one of two treatment groups: Active or Sham treatment. There are sham devices produced that are identical to active devices, only they do not deliver pulsed electromagnetic energy. Randomization will be stratified by surgical procedure in block sizes of 2. The computer-generated randomization lists will be created by the University of California San Diego Investigational Drug Service in a 1:1 treatment group ratio using opaque envelopes. The active and sham devices are indistinguishable in appearance, and therefore investigators, participants, and all clinical staff other than the individual who opens the randomization envelope and chooses a sham or active device will be masked to treatment group assignment for the duration of the data collection period. An Investigational Drug Service pharmacist will open the envelope and provide the investigators with the appropriate device, keeping all investigators masked to treatment group assignment. Upon completion of data collection for a specific subgroup (e.g., amputees, total knee arthroplasty), the pharmacist will provide the investigators with a masked list of the treatment groups (e.g., Treatment A and Treatment B), and the active/sham lists only following analysis for that subgroup, resulting in a triple-masked study (investigators, participants, statistician). Study intervention. The pulsed shortwave device (2 devices, if there are multiple incisions or the incision is larger than the device diameter; 3 devices for total knee and hip arthroplasty or spinal surgery) will be affixed over the primary wound area(s) using tape and activated prior to recovery room discharge (Experimental). The optimal location to treat phantom pain is currently unknown and will partially informed by the results of this pilot study, and patients will be encouraged to move the devices to a new anatomic location until relief is optimized. Supplemental analgesics. In addition to the pulsed shortwave device(s), participants will receive standard-of-care supplemental analgesics which can include acetaminophen, ibuprofen, ketorolac, opioids, gabapentin (this is provider- and patient-dependent). Therefore, all patients of this study-regardless of the treatment arm they are randomized to-will continue to receive current usual and customary analgesia: all will receive the same combination of supplemental analgesics they would regardless of study participation. Participants (and their caretakers) will be provided with verbal and written instructions, and the telephone and pager numbers of an investigator available during business hours throughout the treatment period. Participants can shower with the device in place, but not submerge it during swimming or a bath, as advised by the manufacturer. Participants will be discharged with their pulsed shortwave device(s) in situ and a prescription for immediate-release oral opioid, preferably oxycodone 5 mg tablets, taken for breakthrough pain (surgeons occasionally prefer a different type of opioids such as hydrocodone, which is why we analyze the data using oral oxycodone equivalents). The pulsed shortwave devices will be removed by participants at home following Day 30 when the battery is exhausted (participants may remove them as early as Day 7, if they desire). Removing the devices encompasses tape removal and discarding in the trash (these are disposable, single-use devices). Of note, if a device is reported lost or nonfunctional during the study, it will be replaced by the investigators by mail if more than 7 days of treatment remain. Study outcomes: This is an exploratory pilot study to assist in planning subsequent definitive trials and we therefore have no data analysis plan. We will enroll convenience samples for each of the surgical procedures of up to 30 participants for each procedure, and anticipate analyzing each surgical procedure separately from the others. The two outcomes of primary interest will be (1) the average and worst pain measured with the Numeric Rating Scale (included in the Brief Pain Inventory pain domain), and (2) opioid consumption within the first 7 postoperative days.

Official Title
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Pulsed Electromagnetic Fields for Postoperative Analgesia: A Randomized, Triple-Masked, Sham-Controlled Pilot Study

Conditions
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Postoperative Pain, Acute

Intervention / Treatment
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* Device: Active Pulsed Shortwave Treatment with BioElectronics Model 088
* Device: Sham Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients of at least 18 years of age undergoing one of these primary surgical procedures: non-mastectomy breast surgery with a single-injection paravertebral nerve block laparoscopic cholecystectomy laparoscopic sleeve gastrectomy percutaneous nephrolithotomy ventral hernia repair inguinal hernia repair knee or hip arthroplasty foot/ankle surgery with at least moderate pain anticipated shoulder acromioclavicular joint repair, labral repair, subacromial decompression, or Bankart repair (without rotator cuff repair) hand/forearm/elbow surgery with at least moderate pain anticipated spinal surgery with at least moderate pain anticipated Exclusion Criteria: concurrent use of an implanted pulse generator (e.g., cardiac pacemaker) pregnancy incarceration chronic opioid/tramadol use (daily use within the 2 weeks prior to surgery and duration of use > 4 weeks) neuro-muscular deficit of the surgical area/limb a planned postoperative perineural local anesthetic infusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment: Randomized, Triple-Masked, Placebo-Controlled, Parallel-Arm Human Subjects Clinical Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Pulsed Shortwave Treatment with BioElectronics Model 088<br>Application of 7-30 days of nonthermal, pulsed shortwave (radiofrequency) therapy with BioElectronics Model 088 | Device: Active Pulsed Shortwave Treatment with BioElectronics Model 088<br>* Application of 7-30 days of nonthermal, pulsed shortwave (radiofrequency) therapy with BioElectronics Model 088<br>* Other names: pulsed electromagnetic fields therapy;|
| Sham Comparator: Sham Treatment<br>Application of 7-30 days of a nonfunctional sham device. | Device: Sham Treatment<br>* Application of 7-30 days of a nonfunctional sham device(s)<br>* Other names: Placebo treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. The outcome will the mean value of daily average pain scores measured with the Numeric Rating Scale | Mean value of the average daily pain measured on postoperative days 1, 2, 3, and 7 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. The outcome will the mean value of daily worst pain scores measured with the Numeric Rating Scale | Mean value of the average daily pain measured on postoperative days 1, 2, 3, and 7 | 
| Total OPIOID consumption from recovery room discharge until the data collection phone call on postoperative day 7 (measured in oral oxycodone equivalents) | Total opioid consumption from recovery room discharge until the data collection phone call on postoperative day 7 (measured in oral oxycodone equivalents). | Cumulative opioid consumption queried on postoperative days 1, 2, 3, and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 1 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 2 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 3 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 7 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 14 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 21 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 28 | 
| AVERAGE pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 180 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 1 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 2 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 3 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 7 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 14 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 21 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 28 | 
| WORST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 180 | 
| LEAST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 7 | 
| LEAST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 14 | 
| LEAST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 21 | 
| LEAST pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 28 | 
| CURRENT pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 7 | 
| CURRENT pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 14 | 
| CURRENT pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 21 | 
| CURRENT pain measured with the Numeric Rating Scale | The numeric rating scale is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain scale. | postoperative day 28 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 1 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 2 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 3 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 7 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 14 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 21 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 28 | 
| Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | Opioid consumption of the previous 24 hours (measured in oral oxycodone equivalents) | postoperative day 180 | 
| Brief pain Inventory, short form (interference subscale) | The Brief pain Inventory (short form) is an instrument specifically designed to assess pain and its impact on physical and emotional functioning. The brief Inventory is comprised of three domains: (1) pain, with four questions involving worst, average and current pain levels using a 0-10 numeric rating scale;(2) percentage of relief provided by pain treatments with one question [reported score is the percentage divided by 10 and then subtracted from 10: 0=complete relief,10=no relief] and, (3) interference with 7 questions involving physical and emotional functioning using a 0-10 Likert scale [0=no interference;10=complete interference]: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. This outcome will include the interference subscale. | postoperative day 7 | 
| Brief pain Inventory, short form (interference subscale) | The Brief pain Inventory (short form) is an instrument specifically designed to assess pain and its impact on physical and emotional functioning. The brief Inventory is comprised of three domains: (1) pain, with four questions involving worst, average and current pain levels using a 0-10 numeric rating scale;(2) percentage of relief provided by pain treatments with one question [reported score is the percentage divided by 10 and then subtracted from 10: 0=complete relief,10=no relief] and, (3) interference with 7 questions involving physical and emotional functioning using a 0-10 Likert scale [0=no interference;10=complete interference]: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. This outcome will include the interference subscale. | postoperative day 14 | 
| Brief pain Inventory, short form (interference subscale) | The Brief pain Inventory (short form) is an instrument specifically designed to assess pain and its impact on physical and emotional functioning. The brief Inventory is comprised of three domains: (1) pain, with four questions involving worst, average and current pain levels using a 0-10 numeric rating scale;(2) percentage of relief provided by pain treatments with one question [reported score is the percentage divided by 10 and then subtracted from 10: 0=complete relief,10=no relief] and, (3) interference with 7 questions involving physical and emotional functioning using a 0-10 Likert scale [0=no interference;10=complete interference]: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. This outcome will include the interference subscale. | postoperative day 21 | 
| Brief pain Inventory, short form (interference subscale) | The Brief pain Inventory (short form) is an instrument specifically designed to assess pain and its impact on physical and emotional functioning. The brief Inventory is comprised of three domains: (1) pain, with four questions involving worst, average and current pain levels using a 0-10 numeric rating scale;(2) percentage of relief provided by pain treatments with one question [reported score is the percentage divided by 10 and then subtracted from 10: 0=complete relief,10=no relief] and, (3) interference with 7 questions involving physical and emotional functioning using a 0-10 Likert scale [0=no interference;10=complete interference]: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. This outcome will include the interference subscale. | postoperative day 28 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 1 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 2 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 3 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 7 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 14 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 21 | 
| Awakenings due to pain | The number of times the participant awoke the previous night due to pain | postoperative day 28 | 
| Hospitalization duration measured in days | Day relative to the day of surgery that patient was discharged from the hospital (e.g., same day is postoperative day 0, while the day following surgery is postoperative day 1) | One single measure recorded on or following the day of surgery (whichever day patient is discharged) | 
| Passive flexion (knee and hip arthroplasty patients only) | The number of degrees of passive flexion achieved from a neutral position | One measure take at the two-week postoperative check (approximately postoperative day 14) | 
| Day stopped using intervention | Day relative to the day of surgery that patient stopped using the intervention for (e.g., same day is postoperative day 0, while the day following surgery is postoperative day 1) | One single measure recorded following the day of surgery | 
| Desire use of device in hypothetical future surgery? | Would the patient want to use the device for a hypothetical surgery in the future (yes, no, or undecided)? | queried on postoperative day 28 | 
| Surgical start as recorded using military time format | The time of the surgical incision as recorded using military time format | Intraoperative (within the operating room) | 
| Surgical stop as recorded using military time format | The time of the final suture insertion as recorded using military time format | Intraoperative (within the operating room) | 
| Surgical duration | The time from surgical start to surgical stop measured in minutes and hours | Intraoperative (within the operating room) | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 1 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 2 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 3 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 7 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 14 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 21 | 
| Device location changes | If a patient moves the anatomic location of one or both of the intervention devices (and where the device is moved to) since the last phone contact | Postoperative day 28 |