Effectiveness of Hybrid Form Impulse Therapy (HFIT) Compared to Traditional Transcutaneous Electronic Nerve Stimulation (TENS) in Patients with Chronic Low Back and Knee Pain: A Randomized Controlled Trial

Introduction

Musculoskeletal (MSK) pain is a prominent cause of disability and healthcare costs in the United States. In 2019, MSK disorders affected 127.4 million Americans, making it the third most prevalent disease or injury in the United States.^1–3 Some of the most prevalent forms of MSK pain are low back and knee pain. Chronic low back pain (CLBP) affects over 76 million people in the United States, costing over $100 billion per year.⁴ Frequent knee pain affects almost 25% of adults, with osteoarthritis listed as the most common cause of knee pain in adults over 50 years old.⁵ Furthermore, studies have shown that total knee arthroplasty (TKA) procedures in the United States cost $29,300 on average,⁶ and project the incidence rate of TKA to increase 69% by 2050 compared to 2012.⁷

Clinical guidelines often recommend physical therapy, education, behavioral support, non-steroidal anti-inflammatory drugs, and other conservative care as first-line treatment options.⁸ Conservative treatment options include exercise and education due to both their safety and their impact on outcomes. Results from a meta-analysis of 3514 participants found that exercise and movement reduced lower back pain by an average of 10.7 points out of 100.⁹ Additionally, studies have also shown the effectiveness of pain neuroscience education in improving pain, disability, and kinesiophobia in patients with chronic MSK pain.^10,11 Conservative care has traditionally been provided in-person, but has increasingly become more common through digital health in recent years following the COVID-19 pandemic.^12,13 However, while conservative care is effective, safe, and reduces costs, it is unable to provide immediate or sufficient pain relief for many patients. There is unclear consensus around the use of opioids and injections for chronic pain, which may also often carry harmful side effects.^14–16

Pain physicians and physical therapists often treat MSK pain with transcutaneous electrical nerve stimulation (TENS). However, while traditional TENS devices can act as a temporary treatment for MSK pain, there is little evidence that indicates it to be an effective solution.^17,18 The high amplitudes required for an effective treatment can often be uncomfortable for users. While lower, tolerable amplitudes can provide more comfort due to the temporal summation induced by the wide pulse widths, the treatment effect is reduced. Due to the high impedance of the skin, it is often difficult for adequate electrical current to pass through.¹⁹ Methods to overcome the impedance of the skin include delivering higher voltage to drive sufficient current or faster impulses to bypass the capacitive components of the impedance. A hybrid approach, called Hybrid Form Impulse Therapy (HFIT), combines a fast priming pulse to activate high-threshold nerves, followed by a lower amplitude pulse to achieve temporal summation on a larger group of nerves. By incorporating a short pulse followed by a longer and lower amplitude pulse, HFIT can potentially reduce the discomfort that often comes with traditional TENS.

A feasibility randomized controlled trial (RCT) found that HFIT provided a significant improvement in pain and function in comparison to a sham device among patients with chronic low back pain after four weeks.²⁰ However, little is known about how HFIT performs against traditional TENS. As a result, this study aimed to examine whether HFIT provided improvement in pain and function in comparison to traditional TENS and usual care among participants of a digital chronic MSK program with knee and low back pain. An exploratory objective was to compare engagement between the HFIT, TENS, and usual care groups in the form of number of exercise therapy (ET) sessions completed.

Methods

Study Design

A three-armed, parallel RCT comparing clinical outcomes of Hybrid Form Impulse Therapy (HFIT), traditional Transcutaneous Electronic Nerve Stimulation (TENS), and a comparison group of users who continued usual care in a digital MSK chronic program was conducted. Outcomes were compared at 1, 2, and 4 weeks.

Digital Chronic MSK Program

All study participants received a digital chronic MSK program, which was accessed remotely (Figure 1). The objective of the chronic MSK program was to address participants’ chronic MSK pain through guided support and virtual consultations with health coaches and physical therapists, app-guided exercise therapy (ET) sessions, and educational articles. The program delivered ET and education through “playlists”, which presented three to five exercises specific to back or knee pain. Exercise treatment plans were created by physical therapists following clinical guidelines for care for the indicated condition and focused on a curriculum of stretching, strengthening, balance, and mobility exercises. The curriculum incorporated over 60 distinct exercises, and playlists presented one to two sets of three to ten repetitions, depending on the difficulty level and type of exercise. Members of the chronic MSK app were encouraged to complete exercise playlists at least three times per week. As participants advanced throughout the program, the playlist incorporated more challenging exercises and/or added repetitions. Alongside the ETs, educational articles focused on MSK pain-related topics, including pain neuroscience, movement, treatment options, lifestyle changes, and social support, were delivered.

Figure 1 Digital MSK Application. Abbreviation: MSK, musculoskeletal.

Participants were able to access the chronic MSK program app through smartphones or tablets. In addition to exercise and education, the digital MSK program provided personal support to adhere to the program. Each participant was paired with a personal, certified health coach and physical therapist. Coaches initiated contact with participants via text message and communicated with members asynchronously over time via text message, email, or in-app messaging. Physical therapists assisted participants with tailoring and designing their ET routines as well as providing direct support on exercise form. As an entirely virtual program, participants were able to choose when and where to access the app and its offerings.

Study Participants

In April 2023, individuals participating in the digital MSK program and meeting the inclusion and exclusion criteria based on self-reported information provided in the application were identified. Inclusion criteria were age between 18 and 65 years old; back or knee pain; experiencing pain for at least 12 weeks; Numeric Pain Rating Scale (NPRS) score ≥40 out of 100; joined the digital MSK program after January 1, 2023; completed an ET session or read an educational article every week in the last 3 weeks; provided research consent; and covered by employer’s health plan. Exclusion criteria were diagnosis of cancer or malignant tumors in the last 5 years; back or knee surgery in the last 6 months; current use of a cardiac pacemaker, implanted defibrillator, spinal cord stimulator, pain pump, insulin pump, or any other implanted electronic device; history of opioid, alcohol, or drug use disorder in the last year; cognitive, behavioral, neurologic, or psychiatric disorder; pregnant or plan on becoming pregnant in the next year; epilepsy; or cardiovascular disease.

1853 individuals who met eligibility criteria based on responses to an applicant questionnaire were sent a screener questionnaire containing the exclusion criteria questions above. Of those, 772 (41.7%) responded and were fully assessed for eligibility and 325 (42.1%) were determined to be eligible. The participants deemed eligible for the study provided informed consent to participate in the trial.

Randomization and Blinding

Study participants were randomly assigned to one of three groups, two of which were intervention groups, the HFIT (n=109) or TENS (n=108), or a control group, who received usual care (n=108). Randomization allocation was 1:1:1 and was stratified by pain location (back or knee) using random block sizes of 3, 6, or 9. A research scientist implemented the sequence and assigned the groups with letter codes in order to maintain allocation concealment from the statistician. Research staff enrolled participants and notified participants of their randomization assignment. All analyses were conducted by a statistician who was blinded to group assignment.

Participants randomized to the intervention groups, HFIT and TENS, were given an HFIT device (Enso) (Figure 2) or a traditional TENS (iTENS, LLC) device, respectively. The TENS device used in this study was chosen due to its similarity to the HFIT device, as both were wireless, controlled through an app, and could be attached to the skin through adhesive pads. Both HFIT and TENS group participants were asked to schedule an onboarding call with a study staff member, who provided instructions on how to install the software needed and set up the device. Study staff recommended that intervention participants use their device for at least one hour every day, or as often as needed. Individuals in the usual care group received routine care through the digital MSK program and no devices.

Figure 2 HFIT Device. Abbreviation: HFIT, hybrid form impulse therapy.

After randomization, all study participants were sent a baseline self-report questionnaire, which asked about demographics, clinical characteristics, and outcome variables (eg pain and function), as well as follow-up surveys 1, 2, and 4 weeks after baseline surveys were completed. In order to prevent overlap between surveys at each timepoint, participants were provided one week to respond to each survey before their survey link expired. To ensure participants in the HFIT and TENS groups received their devices in time, devices were shipped after the baseline survey link expired.

Ethical Considerations

The study was approved by the WIRB-Copernicus Group Institutional Review Board (OHRP/FDA IRB registration number IRB00000533) at WIRB-Copernicus Group, registered on ClinicalTrials.gov (NCT05821530), and conducted in accordance with the Declaration of Helsinki. All participants provided informed consent via an online consent form. CONSORT reporting guidelines were followed and are included (Supplementary Material 1).

Measures

The primary outcome was a dichotomous variable of minimal clinically important difference (MCID) in pain improvement (pain MCID), pain based on the response to a clinically validated patient-reported outcome measure: “Over the past 24 hours, how bad was your [back/knee] pain?” with a score from 0 (none) to 100 (worst imaginable). A person achieved a MCID in pain improvement if they showed at least a 23 point or 34% improvement from baseline.²¹

A secondary outcome was a dichotomous variable of MCID in functional improvement (function MCID), created from responses to the validated 11-item Roland Morris Disability Questionnaire (RMDQ-11, back only) and Knee Injury and Osteoarthritis Outcome Score Physical Function short-form (KOOS-PS, knee only). Change from baseline to follow-up was calculated, and function MCID was defined as at least 30% improvement on the RMDQ-11^22,23 or 8-point improvement on the KOOS-PS.^24–26

Additional outcomes were anxiety and depression symptoms. These were measured through the Generalized Anxiety Disorder (GAD-2) and Patient Health Questionnaire (PHQ-2) scores, respectively. Both scales ranged from 0 (none at all) to 6 (most anxious/depressed). A score of 3 or higher was defined as having a positive screen for probable generalized anxiety or depressive disorder.^27,28 Self-reported opioid use was also collected, based on response to the questions: “Have you used any Vicodin^®, OxyContin^®, Norco^®, Hydrocodone, Percocet^®, Methadone, or other opioid painkillers for [back/knee] pain in the past three months?” at baseline.

Engagement outcomes among each group were compared by examining the number of program ET sessions completed, which were tracked through the app. Additionally, study participants were asked to report any adverse events or harms, such as burns, shocks or allergic reactions, to the digital MSK program’s support staff.

Model covariates included age at baseline, gender, pain region (back/knee), education level (high school/some college or associate’s degree/bachelor or advanced degree), general health status (poor/good/very good or excellent), number of comorbidities (hypertension, high cholesterol, asthma, prediabetes, diabetes, and/or osteoarthritis), conservative MSK-related healthcare service use at baseline (physical therapy or MSK-related physician office visits), nonconservative healthcare service use at baseline (MSK imaging or injections), and opioid use at baseline (no/yes).

Data Sources

Baseline data was acquired through the online application at program registration as well as the initial baseline survey. Education level, health status, and comorbidities were based on questions used by the National Health Interview Survey (NHIS). Follow-up surveys and up to two reminders were emailed at 1, 2, and 4 weeks. Respondents received gift cards for $5 at each timepoint for their participation.

Sample Size

Based on a previously conducted feasibility study among digital MSK members with low back and knee pain, differences of 50.8% and 47.0% were detected between the number of HFIT and TENS participants and the number of HFIT and usual care participants, respectively, who achieved pain MCID at Week 4. A more conservative estimate of a difference of 25.0% was used for this study’s sample size calculations. Assuming 80% statistical power and 2.5% significance level to account for the two comparisons, a sample size of 72 per arm, or 216 total, was required to detect a 25.0% difference between groups in pain MCID. Allowing for 30% attrition, we aimed to recruit at least 281 participants.²⁹

Statistical Analysis

Baseline demographic and clinical characteristics were presented as frequencies and percentages or means and standard deviations (SD). Descriptive statistics reported at 1, 2, and 4 weeks included the number and percentage of participants who achieved MCID in pain and function at follow-up compared to baseline. The percentage of participants who screened positive for anxiety and depression symptoms in each group were compared. To assess the differences among groups, chi-square tests were conducted, along with pairwise proportions tests, where Hochberg adjustments were used to adjust for multiple comparisons.

Unadjusted and adjusted logistic generalized estimating equations (GEE) methods were used to compare the effects of each treatment on primary and secondary outcomes. Covariates were controlled for by including baseline age, gender, pain region, education level, general health status, number of comorbidities, conservative healthcare service use (physical therapy or physician office visits), nonconservative healthcare service use (imaging or injections), and opioid use in the model. Between-group differences were assessed with a group × time interaction effect, with time as a categorical variable. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated.

An exchangeable correlation structure was used to adjust for correlated observations. Missing data were addressed using multiple imputation analysis, assuming data were missing at random (MAR). The primary analysis employed study participants who adhered to the study protocol, defined as having used their device at least 3 days in the last week at all three follow-up timepoints, in a per-protocol analysis. Dropouts, non-compliant subjects, and protocol violations were included in an intention-to-treat analysis. All analysis was performed in R (version 4.0.5; R Foundation for Statistical Computing).

Results

Figure 3 reports the volume of subjects in the HFIT, TENS, and usual care groups at each stage throughout the study. Of the randomized participants, 100 (91.7%), 95 (88.0%), and 93 (86.1%) participants completed the initial baseline survey in the HFIT, TENS, and usual care arms, respectively, and 90 (82.6%), 86 (79.6%), and 87 (80.6%) participants completed the final follow-up survey in the HFIT, TENS, and usual care arms, respectively (Figure 3).

Figure 3 CONSORT Flowchart.

Sample Characteristics

Baseline characteristics of all randomized participants (n=325) are shown in Table 1. Baseline characteristics are comparable between participants in each group. Participants had a mean age of 50.0 (SD 9.8) years, with 75.7% enrolled in the digital MSK program for back pain and 24.3% for knee pain. At the time of program registration, study participants had a mean baseline pain score of 59.8 (SD 12.1), out of 100.

Table 1 Baseline Characteristics of Randomized Participants

Baseline characteristics of participants who responded to the baseline questionnaire (n=288) are shown in Table 2. Participants who responded had a mean age of 50.3 (SD 9.8) years, with 75.7% enrolled in the program for back pain and 24.3% for knee pain. At the time of program registration, participants had a mean baseline pain score of 59.8 (SD 11.9), out of 100. 67.0% were White, 8.7% were Black or African American, 6.9% were Asian, 0.7% were American Indian or Alaska Native, and 15.3% were other single and multiple races.

Table 2 Baseline Characteristics of Randomized Participants Who Completed Baseline Questionnaire

Primary Outcome

The percentage of participants achieving MCID in pain improvement was 5.9% higher for the HFIT group versus the TENS group at 1 week, 12.8% at 2 weeks, and 14.1% at 4 weeks (Table 3). The percentage achieving MCID in pain improvement was 10.5% higher for the HFIT group versus the usual care group at 1 week, 20.3% at 2 weeks, and 12.9% at 4 weeks. At Week 4, there was no significant difference in the percentage of participants achieving MCID in pain (p=0.126) or functional (p=0.887) improvement among the groups.

Table 3 Outcome Measures by Group Over Time

Figure 4 shows results from unadjusted and adjusted models for the primary outcome from the per protocol analysis. In adjusted models, we observed significantly lower odds of achieving a MCID in pain improvement at 4 weeks for the TENS (OR: 0.42, 95% CI: [0.19, 0.92]) and usual care groups (OR: 0.35, 95% CI: [0.18, 0.72]), compared to the HFIT group. In intention-to-treat findings, the adjusted model showed significantly lower odds of achieving a MCID in pain improvement at 4 weeks for the usual care group (OR: 0.47, 95% CI: [0.26, 0.83]), compared to the HFIT group (Figure 5).

Figure 4 Per-protocol results: adjusted ORs (95% CI) of pain and function MCID at Week 4 (reference: HFIT). Abbreviations: OR, odds ratio; MCID, minimal clinically important difference; TENS, transcutaneous electrical nerve stimulation; HFIT, hybrid form impulse therapy.

Figure 5 Intention-to-treat results: adjusted ORs (95% CI) of pain and function MCID at Week 4 (reference: HFIT). Abbreviations: OR, odds ratio; MCID, minimal clinically important difference; TENS, transcutaneous electrical nerve stimulation; HFIT, hybrid form impulse therapy.

Secondary Outcomes

The percentage of participants achieving MCID in functional improvement was higher for the HFIT group versus the TENS group by 11.3% at Week 1, 5.5% at Week 2, and 3.5% at Week 4. The percentage achieving MCID in functional improvement was higher for the HFIT group versus the usual care group by 2.3% at Week 1 and 0.6% at Week 4 (Table 3).

Adjusted model results from the per-protocol analyses showed lower odds of achieving MCID in functional improvement at 4 weeks for the TENS (OR: 0.49, 95% CI: [0.21, 1.12]) and usual care groups (OR: 0.76, 95% CI: [0.35, 1.7]), compared to the HFIT group. However, the findings were not significant in per-protocol (Figure 4) or intention-to-treat (Figure 5) analyses.

Of the participants who responded to the baseline survey, 21.0%, 14.0%, and 15.8% of HFIT, TENS, and usual care users screened positive for anxiety symptoms, respectively. About 9.0%, 3.2%, and 8.4% of HFIT, TENS, and usual care users screened positive for depression symptoms, respectively. At Week 4, fewer HFIT users screened positive for anxiety symptoms (8.0%) than TENS (10.5%) and usual care (9.6%) users. Fewer TENS users screened positive for depressive symptoms (4.7%) than HFIT (6.9%) and usual care (7.0%) users. No significant differences were detected among groups for anxiety or depression outcomes.

Exploratory Outcomes

Engagement was evaluated by collecting the number of ETs completed. Between May and October 2023, the HFIT, TENS, and usual care groups averaged 66.6 (SD: 58.9; range 1–277), 46.0 (SD: 45.9; range: 2–349), and 74.3 (SD: 56.8; range: 1–305) ET sessions, respectively. Both HFIT and usual care users completed significantly more ETs than TENS users (p=0.026 and p=0.002, respectively). No statistically significant difference was detected between the HFIT and usual care groups (p=0.586). Throughout the duration of the study, no adverse events were reported among study participants.

Discussion

To our knowledge, this is the first RCT to utilize a hybrid form impulse therapy for the treatment of chronic low back and knee pain. As first-line treatments, including exercise, education, and healthy behavior change, are essential to improving MSK pain, this study ensured that all study participants were enrolled and engaged in a digital MSK program providing these treatments. This study aimed to evaluate whether any additional treatments, such as HFIT or TENS, added value in addition to PT-guided exercise, education, and healthy behavior change coaching.

Results from this study suggest HFIT is more effective than traditional TENS and usual care in terms of achieving a clinically meaningful pain improvement. Analyses showed that more HFIT users achieved a minimal clinically important difference in pain than both TENS and usual care users as a trend over time. Primary analysis found that after adjusting for multiple covariates, among users who actively engaged with their devices, participants who were in the HFIT group had 2.3 times and 2.8 times the odds of achieving meaningful pain improvement compared to participants in the traditional TENS and usual care groups, respectively. While there is limited research around the use of HFIT in treating chronic pain, literature on the effectiveness of traditional TENS in pain management has been inconsistent. Results from a qualitative synthesis study of four RCTs found that TENS was unreliable in demonstrating benefits to chronic low back pain.³⁰ Several meta-analyses provided a similar conclusion, with results presenting little or no evidence to support the use of TENS among patients with chronic low back pain.^31,32 The results of this study are consistent with these findings, as traditional TENS users showed little difference in pain improvement compared to usual care users at Week 4 (34.7% versus 35.9%, respectively).

This study also found that both HFIT and usual care users had significantly higher engagement in exercise than traditional TENS users. We recruited members who were already actively engaged in the digital MSK program; however, we saw that members with HFIT continued to complete their exercises, while TENS users slowed down on their progress. Furthermore, no significant difference was detected between the number of ETs completed between HFIT and usual care users, suggesting that the difference in pain improvement between the two groups is due to the effects of the HFIT device rather than exercise alone.

This study did not detect significant differences in function, anxiety, or depression symptoms. However, anxiety and depression were low among study participants at baseline and therefore may not have had room to improve substantially. Furthermore, as exercise has consistently been shown to have a positive impact on mental health among patients experiencing back pain,^9,33–35 it is possible that this study did not detect substantial differences in these outcomes from adding in a pain-relief device alone, as all participants in this study had access to exercise therapy. Lastly, the insignificant findings of secondary outcomes may also be due to the study being powered to detect differences only in the primary outcome, a clinically meaningful improvement in pain.

There are multiple inherent advantages to HFIT therapy, including its ability to provide local, immediate pain relief while being minimally invasive and portable. Additionally, as a non-drug-based therapy, HFIT avoids the adverse side effects that opioids can cause, such as drowsiness, addiction or dependence, constipation, and impairment in overall function.³⁶ Research evidence strongly supports conservative therapies, such as exercise and cognitive behavioral therapy, as a way to work towards sustained improvements in pain.^37,38 As a result, HFIT should not be a replacement for exercise therapy and other first-line treatments, but can be used to supplement and support them by providing patients with additional pain relief. This study confirmed that users who were assigned to the HFIT arm continued to complete their exercise sessions.

This study’s strengths include its rigorous design as a three-arm, single-blinded RCT, where the analyst was blinded to treatment assignment. The study included participants experiencing both back or knee pain, which provides more generalizability. Additionally, the TENS unit selected for the study was similar in design to the HFIT device. Both devices were wireless, attached to the skin using an adhesive pad, and controlled through an app, which reinforces that the difference in pain improvement between the two devices is due to the difference in the electrical stimulation rather than the usability of the device or sham effects of the device application. Lastly, this study imposed a strict definition of MCID in pain of at least a 23 point or 34% improvement from baseline, while several studies have considered 10–17 points to be a clinically meaningful difference in chronic musculoskeletal pain.^39,40

Limitations of this study include the lack of blinding among the participants. However, this was not feasible given the packaging differences between devices. Given the variability in shipping times for the pain relief devices, the follow-up timepoints of 1, 2, and 4 weeks are approximate. The study was unable to control for whether participants’ pain improved or worsened between the time they joined the digital MSK program and the start of the study. Lastly, to evaluate the effects of each treatment among users who adhered to the study protocol, the analysis employed a per-protocol analysis, which is underpowered, as the primary analysis. However, we also included the results of the intention-to-treat analysis, which is sufficiently powered and contains less bias.

Findings from this study suggest that HFIT improves pain and encourages more engagement with exercise therapy compared to both traditional TENS and usual care. Future studies will examine the effects of HFIT among patients experiencing pain in other locations, such as shoulder or hip. Future work will also evaluate clinical outcomes at longer follow-up time points to evaluate sustained relief.

Conclusion

More participants of a digital MSK program who were randomized to use the HFIT device experienced meaningful pain improvement at four weeks versus participants who used a traditional TENS device and participants who continued usual care. Among participants who adhered to the study protocol, study results found that HFIT users had significantly higher odds of achieving a minimal clinically important difference in pain at four weeks compared to traditional TENS and usual care users. Findings suggest that the efficacy and ease of use of HFIT can serve as an alternative solution to pharmaceutical treatments as well as a complement to first-line treatments to improve pain management among patients with chronic low back and knee pain.