Pulsed Electromagnetic Fields for Post-Amputation Pain

Pulsed Electromagnetic Fields for Post-Amputation Pain: A Randomized, Triple-Masked, Sham-Controlled, Crossover Pilot Study

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 chronic post-amputation pain with nonthermal, pulsed shortwave (radiofrequency) therapy, optimize the study protocol, and estimate the treatment effect in preparation for developing subsequent definitive clinical trials.

Study Overview

• Status: Completed
• Conditions: Phantom Limb Pain; Residual Limb Pain
• Intervention / Treatment: Device: Active then Sham Treatment; Device: Sham then Active Treatment

Detailed Description

The proposed study will be a randomized, participant- and observer-masked, sham-controlled, crossover, 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 for post-amputation phantom and residual limb pain.

Specific Aim 2: To estimate the treatment effect of adding nonthermal, pulsed shortwave therapy to usual and customary analgesia for post-amputation phantom and residual limb pain. This will provide an idea of the optimal amputee characteristics amenable to this analgesic technique and allow determination of the required sample sizes of subsequent definitive clinical trials.

Hypothesis: Nonthermal, pulsed shortwave therapy will decrease pain in the 28 days following application for post-amputation pain.

This will be a single-center (University of California San Diego), randomized, participant- and observer-masked, sham-controlled, crossover human subjects pilot study.

Enrollment. Participants will be consenting adults experiencing post-amputation phantom and/or residual limb pain. Study inclusion will be proposed after an amputee contacts the investigators. 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).

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 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, 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 devices used are over-the-counter (Model 088, BioElectronics, Frederick, Maryland) and 2 devices (both the same treatment group) will be shipped to the patient either in or out of California who will then contact an investigator for assistance in self-placement of the device on the residual limb. 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 every two days until relief is experienced.

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 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.

Amputees will return their initial devices in pre-addressed and -stamped envelopes that we provide. They will be sent a second device which is the opposite treatment of the initial device: participants who initially received sham will subsequently receive active, and vice versa. These will be applied on (approximately) Day 35 and the same protocol will be repeated as for the initial device, with additional data collected for 35 days after placement of the second device. The second device will be discarded in the trash.

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.

Primary end points: This is an exploratory pilot study to assist in planning subsequent definitive trials and we therefore have no data analysis plan. We will enroll a convenience sample of up to 40 participants. The outcome measures of primary interest will be (1) the change in "average" residual and phantom limb pain scores between baseline and Day 28 of the initial treatment, as well as (2) the Patient Global Impression of Change on Day 28 of the initial treatment.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Univerity of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult patients of at least 18 years of age [19 years in Alabama and Nebraska]
• with an upper or lower limb amputation at least 12 weeks prior to enrollment distal to the shoulder or hip (femoral head remaining), respectively, and including at least one metacarpal or metatarsal bone, respectively
• experience at least moderate residual and/or phantom limb pain-defined as a 3 or higher on the Numeric Rating Scale (NRS; 0-10, 0= no pain; 10=worst imaginable pain)-at least daily for the previous 2 months
• willing to avoid both changes to their analgesic regimen as well as elective surgical procedures for 70 days after initiation of treatment with PEMF therapy

Exclusion Criteria:

• concurrent use of an implanted pulse generator (e.g., cardiac pacemaker)
• pregnancy
• incarceration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active then Sham Treatment; Application of 30 days of nonthermal, pulsed shortwave (radiofrequency) therapy, 7 day "washout", 30 days of sham.	Device: Active then Sham Treatment; Application of 30 days of nonthermal, pulsed shortwave (radiofrequency) therapy; then sham treatment after a 7-day "washout" period; Other Names: nonthermal, pulsed shortwave (radiofrequency) therapy then sham; pulsed electromagnetic fields therapy then sham
Experimental: Sham then Active Treatment; Application of 30 days of a nonfunctional sham device, 7 day "washout", then 30 days of nonthermal, pulsed shortwave (radiofrequency) therapy	Device: Sham then Active Treatment; Application of 30 days of sham treatment; then 30 days of nonthermal, pulsed shortwave (radiofrequency) therapy after a 7-day "washout" period; Other Names: Sham then nonthermal, pulsed shortwave (radiofrequency) therapy; Sham then pulsed electromagnetic fields therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in average RESIDUAL limb pain scores between baseline and Day 28 of the initial treatment as 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 be the difference between the baseline and Day 28 timepoints.	Baseline and Day 28
Change in average PHANTOM limb pain scores between baseline and Day 28 of the initial treatment as 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 be the difference between the baseline and Day 28 timepoints.	Baseline and Day 28
Patient Global Impression of Change for RESIDUAL limb pain between baseline and Day 28 of the initial treatment	A 7-point Likert scale with 1 equivalent to "much worse", 4 equivalent to "no change", and 7 equivalent to "much improved". Patients compare their current pain level with baseline using this scale.	Day 28
Patient Global Impression of Change for PHANTOM limb pain between baseline and Day 28 of the initial treatment	A 7-point Likert scale with 1 equivalent to "much worse", 4 equivalent to "no change", and 7 equivalent to "much improved". Patients compare their current pain level with baseline using this scale.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change for RESIDUAL limb pain	A 7-point Likert scale with 1 equivalent to "much worse", 4 equivalent to "no change", and 7 equivalent to "much improved". Patients compare their current pain level with baseline using this scale.	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Patient Global Impression of Change for PHANTOM limb pain	A 7-point Likert scale with 1 equivalent to "much worse", 4 equivalent to "no change", and 7 equivalent to "much improved". Patients compare their current pain level with baseline using this scale.	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Change in AVERAGE RESIDUAL pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Change in WORST RESIDUAL pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Change in LEAST RESIDUAL pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 28 and 35 for both initial and crossover treatments
Change in CURRENT RESIDUAL pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 28 and 35 for both initial and crossover treatments
Change in AVERAGE PHANTOM pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Change in WORST PHANTOM pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Change in LEAST PHANTOM pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 28 and 35 for both initial and crossover treatments
Change in CURRENT PHANTOM pain from baseline 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 difference between the baseline and current pain level measured with the Numeric Rating Scale	Days 28 and 35 for both initial and crossover treatments
As-needed (non-scheduled) analgesic use	Patient's perception of requirements over the previous 24 hours of as-needed (non-scheduled) analgesic use	Inquired on Day 2, 4, 7, 21, 28 and 35 for both initial and crossover treatments
Brief pain inventory, short form (interference sub scale)	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.	Inquired on Days 28 and 35 for both initial and crossover treatments
Awakenings due to pain the previous evening	The number of awakenings due to pain that occurred the previous evening	Inquired on Days 2, 4, 7, 21, 28, and 35 for both initial and crossover treatments
Does patient want to continue using device?	Does the patient want to continue using device answered as "yes", "no" or "unsure"	Inquired on Day 35 for both initial and crossover treatments
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 contact	Inquired on Days 2, 4, 7, 21, 28 and 35 for both initial and crossover treatments

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Brian Ilfeld, MD, MS, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Actual): August 10, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Pain, Postoperative; Phantom Limb
• Other Study ID Numbers: PEMF Amputee Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes