Plantar Fascititis

Plantar Fascititis Study

Use of ActiPatch for Treatment of Plantar Fasciitis

Principle Investigator:
Joel Brook, DPM,MS,FACFAS
Associate or Co-Investigators
Morley A. Herbert, PhD
Damien M. Dauphine, DPM, FACFAS, CWS
Nicole D. Hancock, DPM
D. Jason Hancock, DPM
Jaryl G. Korpinen, DPM
Study Co-Coordinator
Tracey Hawkins, RN

 

Executive Summary

 

Purpose

To assess whether patients using ActiPatch stimulators at night for treatment of plantar fasciitis have reduced usage of pain medications, while maintaining an adequate control of their pain.

Design

A double blind, randomized prospective study covering a 7 day treatment period. Patients were trained in use of stimulator and supplied with data forms to record their pain level (VAS) upon awakening and at night. They also kept a log of medication used.

Study was approved by North Texas Institutional Review Board at Medical City Dallas in August 2008.

Analysis of Medication Usage

All medications were translated into ‘doses’ using multiples of the base concentration (ibuprofen 200 mg, acetominophen 250 mg).

Results

70 patients have been enrolled to date, with 28 controls and 42 stimulator units. Repeated measures ANOVA is statistically significant for a difference in time response between the ‘stim’ and ‘cont’ groups (p =0.02). The evening VAS shows no difference between groups.

Graph 3 show medication doses for the two groups over the 7 days. There is a large clinically significant difference in usage. In the ‘stim’ group, no mediation was used on 82.3% (242/294) of the patient-days while no medication was used in ‘cont’ group on 68.4% (134/196) of the patient-days (p < 0.001). On days 3 and 4, there was a strong trend to reduced usage by the ‘stim’ group (p=0.07) while on day 7, the difference was larger (p=0.06).When total medication over days 1-4 is compared, the ‘stim’ group uses less than 1/2 that of the controls, while over the full 7 days, total medication usage drops by 55%. Large variances in usage preclude significant p-values with current enrollment levels.

No study related adverse events were reported by any patient.

Discussion


The study shows that using the stimulator at night leads to a steadily increasing reduction of morning pain even though the patients use less than 1/2 the medication doses of the control group.

Background

Plantar Fasciitis (PF) is a painful inflammatory condition caused by excessive wear to the plantar fascia of the foot or biomechanical faults that cause abnormal pronation of the foot. The plantar fascia is a band of connective tissue on the underside of the foot stretching from the heel to the toes. The illustration shows typical locations of the pain. Patients suffering from PF often have extreme pain on taking their first steps in the mornin

PF accounts for approximately 15% of all foot related complaints (Lutter, 1997, Med. J Allina. 6(2) http://www.allina.com) seen by clinicians.

While many different treatments have been effective, any relief may be slow in coming as it typically takes six to eighteen months to find a favorable resolution; overall plantar fasciitis has a generally good long-term prognosis. The mainstays of treatment are stretching the Achilles tendon and plantar fascia, resting, keeping off the foot as much as possible, discontinuing aggravating activity, cold compression therapy, contrast bath therapy, weight loss, arch support and heel lifts, and taping. Care should be taken to wear supportive and stable shoes. Patients should avoid open-back shoes, sandals, “flip-flops”, and any shoes without a raised heel. To relieve pain and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are often used but are of limited benefit. Diclofenac is sometimes prescribed for ongoing problems. Patients should be encouraged to lessen activities which place more pressure on the balls of their feet because it increases tension in the plantar fascia. This is counter-intuitive because the pain is in the heel, and the heel is often sensitive to pressure which causes some patients to walk on the balls of their feet.

Local injection of corticosteroids often gives temporary or permanent relief, but may be painful, especially if not combined with a local anesthetic and injected slowly with a small-diameter needle. Recurrence rates may be lower if injection is performed under ultrasound guidance. Repeated steroid injections may result in rupture of the plantar fascia. This may actually improve pain initially, but has deleterious long-term consequences.

It is estimated that 25 million patients experience acute pain caused by trauma or surgical procedures each year. The most commonly prescribed analgesics for acute pain are NSAIDs, acetaminophen, and opioids; however in the peri-operative period NSAIDs are often contraindicated due to their anticoagulant effects. Acetaminophen is not the drug of choice except in a small number of patients in whom other drugs are contraindicated, due to its lack of an anti-inflammatory effect. Opioids, which are frequently used in the perioperative period2 are problematic in ambulatory patients due to their CNS effects, and they also have no anti-inflammatory properties and thus do not minimize edema.

PEMF in some form has been used or investigated since the work of Ginsberg in 1934 when he pulsed the emission of a medical diathermy machine to elicit a non-thermal biological effect Since this pioneering work, PEMF therapeutic applications have been reported for the reduction of post-traumatic and post-operative pain and edema in soft tissues, wound healing, burn treatment, and nerve regeneration (Pilla et al., 1993; Itoh et al., 1991; Ionescu et al., 1982; Raji and Bowden, 1983). Ten years ago, an NIH Consensus Conference Report on Electromagnetic Fields in Medicine (1998), entitled “An Assessment of Health Effect from Exposure to Power-Line Frequency Electric and Magnetic Fields” concluded in an over 500 page report (NIH Publication 93-3981, Washington, DC) that the one area where there was overwhelming evidence for beneficial effects of electromagnetic fields was the stimulation of bone healing in orthopedics. An Army study of ankle sprains showed that PEMF exposures are generally in a range of 15 to 45 minutes with significant reductions in pain and edema usually occurring during, or immediately after, treatment (Pennington et al., 1993; Wilson, 1974). The clinical outcome of effective treatment of pain and edema is a more rapid return to function post trauma, as well as enhanced healing of pathologies, such as ischemic ulcers (Hunt et al., 1986).

There is a large body of clinical experience that has led to the recognition of pulsed electromagnetic therapy as an effective treatment for tissue trauma, both accidental and postoperative, especially during the early stages. In a study combining PEMF with ice as treatment after radial fractures the group using the stimulation showed increased improvement in their VAS scores over the 3 treatment days compared to scores in the ice alone group (Cheing GLY, Wan JWH and Lo SK: “Ice and pulsed electromagnetic field to reduce pain and swelling after distal radius fractures”. J Rehabil Med 2005; 37: 372-377). In a study of 40 outpatients with documented radiographic evidence of osteoarthritis and pain, PEMF stimulation led to statistically significant reduction in pain scores measured after therapy (5 days for 20 min/day) and at 30 days compared to scores before therapy (Alcidi L, E, Maresca BM, Santosuosso U, Zoppi M: “Low power radiofrequency electromagnetic radiation for the treatment of pain due to osteoarthritis of the knee”. Reumatismo, 2007; 59(2):140-145). In a small group of patients with fibromyalgia pain, twice daily treatments of 40 min for 7 days, led to decreases in reported VAS scores for the treated patients (Thomas AW, Graham K, Prato FS, McKay J, Forster PM, Moulin DE, Chari S: “A randomized, double-blind, placebo-controlled clinical trial using a low-frequency magnetic field in the treatment of musculoskeletal chronic pain”. Pain Res Manag 2007; 12: 249-58.). In a post-operative study of patients having arthroscopic surgery on their knee cartilage treatment consisted of using the stimulator for 90 days for 6 hours/day. Patients in the stimulated group scored higher on the Knee injury and Osteoarthritis Outcome Score and recorded use of less NSAID pain medications at 45 and 90 days (Zorzi C, Dall’Oca C, Cadossi R, Setti S: “Effects of pulsed electromagnetic fields on patients’ recovery at’ter arthroscopic surgery: prospective, randomized and double-blind study”. Knee Surg Sports Traumatol Arthrosc 2007; 15:830-4). Post-operative pain reduction was noted in a study by Hedeh P and Pilla AA (Effects of Pulsed Electromagnetic Fields on Postoperative Pain: A Double-Blind Randomized Pilot Study in Breast Augmentation Patients. Aesth Plast Surg 2008; E-pub May28) using a similar device from another company. They found significant decreases in the reported VAS scores in women after breast augmentation using stimulators to supplement any pain medication. Pain medication usage (pills consumed) per day, dropped significantly faster in the stimulator group.

Since stimulation techniques have been used for a long period of time and their appear to be no reports in the literature of adverse events using the different stimulation modalities, stimulation at the levels used in these studies is likely safe,

The mechanism by which PEMF works on controlling pain is not well understood although pain levels may be affected by its enhancement of nitric oxide (NO) release, a short-lived signaling molecule known to be involved in anti-inflammatory cascades. NO is also an inhibitor of the proinflammatory pathways that produce endothelin-1 and IL-1. (Miura M, Takayama K, Okada J: Increase in nitric oxide and cyclic GMP of rat cerebellum by radio frequency burst-type electromagnetic field radiation. J Physiol 1993; 461: 513-524. Diniz P, Socjima K, Ito G: Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation. Nitric Oxide 2002; 7:18-23. Schnoke M, Midura RJ: Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: comparison to parathyroid hormone and insulin. J Orthop Res 2007; 25:933-940. Fitzsimmons RJ, Gordon SL, Kronberg J, Ganey T, Pilla AA.: A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling. J Orthop Res 2008; 26: 854-9. Morimoto S, Takahashi T, Shimizu K, Kanda T, Okaishi K, Okuro M, Murai H, Nishimura Y, Nomura K, Tsuchiya H, Ohashi I, Matsumoto M: Electromagnetic fields inhibit endothelin- I production stimulated by thrombin in endothelial cells. J Int Med Res 2005; 33:545-554. Jeong JH, Kum C, Choi HJ, Park ES. Sohn UD: Extremely low frequency magnetic field induces hyperalgesia in mice modulated by nitric oxide synthesis. Life Sci 2006; 78: 1407-1412)

ActiPatch

Like other pulsed electromagnetic therapy devices ActiPatch Therapy functions at a frequency in the 27.1 MHz ISM band. The electromagnetic field has the (vector) form of the “near-field” produced by a loop antenna. Long-range transmission (“far-field” effect) is rendered negligible by the small antenna size, compared with one wavelength. The near field induces electric current in human tissue, oscillating at such a high frequency that it cannot be “felt” by our nervous system. The high frequency also limits penetration by way of the “skin-effect”,

resulting in a “skin depth” of approximately 10 cm. In addition, the geometry of the loop limits penetration to approximately one diameter, (or approximately, the width, in the case of the model 250). So antenna size dominates penetration over skin effect for the model 250 and 500.

The ActiPatch affixes onto patient for a convenient 24-hour treatment, with an “overnight” suggested minimum treatment time. Therapeutic efficacy requires consideration of the treatment time difference factor. ActiPatch Therapy Device produces a 24 hour absorbed energy of 630 mJ/cc compared to traditional pulsed electromagnetic devices which produce a 15 minute absorbed energy in the range of 110 mJ/cc at the 1.5 watt power setting This suggests that a 6 to 8 hour ActiPatch Therapy treatment is well within the range of efficacy for soft tissue injuries.

ActiPatch™ Therapy power density at the skin surface is between 14 and 73 ?W/cm². It is reasonable to assume that 10% of the incident energy is absorbed in the first centimeter of tissue depth, or maximum energy absorption of up to 7.3uW/cm3 in skin. While that absorbed power appears to be a very low exposure level, in fact, this level is well above the threshold levels necessary to ensure non-thermal biological responses from electromagnetic field exposures. To understand this statement it is important to note that non-thermal effects of electromagnetic field exposure are due to the induced electric field in the tissue and not the magnetic field. ActiPatch produces an induced electric field of typically 10 milliVolt/cm. In a fibroblast/collagen wound healing model, field intensities as low as 30 ?V/cm rms were sufficient to significantly reduce protein excretion by cells (consistent with a reduction in edema and scarring) for exposure durations of 12 hours (McLeod, et a l. 1987). This field intensity corresponds to an induced power level of 10-11 Watts/cm3. More recently, investigations on other aspects of cell phenotypic expression related to the healing process, including differentiation, cell morphologic adaptation, and cell motility, suggest that even this very low exposure level can be further reduced by extending the exposure time. In a study on morphologic adaptation of cells to induced electromagnetic fields, 3.5 ?V/cm rms electric fields were found to be sufficient to induce significant morphologic changes if the exposure times were extended to 24 hours, corresponding to induced power levels of 10-13 Watts/cm3 (Lee &

McLeod, 2000). Moreover, a study on regulation of differentiation in mesenchymal cells, utilizing exposure durations of up to 64 hours, showed that cells were capable of responding to induced field intensities as low as 0.7 ?V/cm rms, corresponding to induced power densities of 5×10-15 Watts/cm3 (McLeod & Collazo, 2000). It is clear, therefore, that use of ActiPatch™ Therapy, resulting in adsorbed power levels in the range of 7.3 ?W/cm3, provides field exposure levels at the target tissue that are five to nine orders of magnitude above the thresholds which have been established for non-thermal electromagnetically induced biological effects at the cell and tissue level.

The ActiPatch™ has received FDA approval for use in reducing swelling after blepharoplasty. In Canada, Health Canada has approved it for relief of pain in musculoskeletal complaints. The system also has EU approval as a Class II pulsed electromagnetic medical device. On-going studies (including this one) will provide clinical data to support further applications for the device.

The purpose of this study is to investigate pulsed electromagnetic frequency (PEMF) for the treatment of pain in patients with diagnosed plantar fasciitis.

Study Executions

Study Design

  • The study is a prospective randomized double-blind, placebo-and positive- controlled trial of PEMF versus placebo for pain in adult patients having diagnosed plantar fasciitis
  • 70 patients:42 control and 28 active
  • Control simulators will be identical but inactive as far as output signal
  • Patients will wear device nightly for 7 days with loop antenna placed adjacent to area of pain on the bottom of the foot
  • Patients given a Visual Analogue Scale (VAS) to fill out am and pm each day
  • Patients given form to record pain meds used
  • No new treatment to be started during study unless patient drops out
  • Return filled out data forms to coordinator
  • All study personnel will be trained to use the stimulator and in the use of the VAS scores

Inclusion/Exclusion Criteria

  • All patients with diagnosis of plantar fasciitis agreeing to participate
  • Over 18 years old
  • Able to wear unit and keep data up-to-date

Recruitment of Patients

Patients seen in clinician’s office, discuss study, and consent

Blinding
Blinding method was double blinding, all devices – active and control, were given numbers and packaged in the same box, without any sign on the package. The code for active/control stimulators was sent to Dr. Morley Herbert only after the entire data was collected, so he can analyze data. Dr. Morley Herbert was the only investigator to receive the codes list. All devices (active and control) had the same physical appearance, wrapped in the exact same wrap and had red light when working. Since the stimulation could not be felt, there was no way to separate groups.

Randomization

140 boxes (70 active and 70 control) were delivered to the center, and were tossed into cardboard boxes, mixing active and control devices together. Trial patients just picked one out of the box. The mixing process of the active and control together was probably not perfect, giving us a bit more patients on active device, then on control.

Adverse Events Reporting

As mentioned in the informed consent forms, all adverse events were reported to investigating physicians, where they needed to report adverse events to study Co-coordinator, Tracey Hawkins. Patients were given phone numbers of their physician, the principle investigator and Tracey Hawkins.

Administrative Section
The location and personnel of study related activities:

Study Activity Location Study Personnel
Recruiting - Medical City, 7777 Forest Lane, Dallas, TX- Baylor Plano, 4708 Alliance Blvd, Plano, TX- Complete Foot and Ankle Care of North Texas

2817 S. Mayhill Rd, Denton, TX

- 500 North Valley Pkwy, Lewisville, TX

- 6309 Preston Rd, Plano TX

Dr. Joel BrookDr. Damien M. DauphineDr. Nicole D. Hancock

Dr. Jason Hancock

Dr. Jaryl Korpinen

Signing patients on informed consent Same as recruiting locations Dr. Joel BrookDr. Damien M. DauphineDr. Nicole D. Hancock

Dr. Jason Hancock

Dr. Jaryl Korpinen

Treatment/Device and forms allocation Same as recruiting locations Dr. Joel BrookDr. Damien M. DauphineDr. Nicole D. Hancock

Dr. Jason Hancock

Dr. Jaryl Korpinen

Data Collection 3626 Lakeside Dr. Rockwall, TX Tracey Hawkins, RN
Data Analysis Dr. Herbert’s Home Office – Dallas, TX Dr. Morley Herbert

Data Collection
Measurements were done by the patients who filled out daily log sheets recording morning and evening pain levels on the VAS line, and all daily pain meds used. The data was collected by Tracey Hawkins, RN (study coordinator) who transferred it to a spreadsheet and forwarded it on to Dr. Morley Herbert for analysis at the end. Seven data forms came back to her at the last minute and Dr. Morley Herbert entered the values himself.

Statistical Analysis


Data was collected from the patients at the end of their participation. They had kept logs which included the VAS (Visual Analog Score) pain assessment, as rated upon first getting out of bed, and at night before going to bed. They also marked down all pain medication used including brand, strength and dosage.

The monitor copied the data from the individual sheets and placed it in a spreadsheet with one row per patient. Data was combined so that one column was used each day. At the end of the study the data was provided for analysis.

The data was read into SAS (V9.2, SAS Institute, Cary, NC) by DDE link. The contents of the daily cells was parsed to create morning VAS, evening VAS and medication usage values. Medication was scored in units based on 200 mg ibuprofen, 250 mg naproxen or 250 mg acetaminophen as 1 unit. One tablet of Celebrex was also scored as 1 unit.

Basic summary statistics were run for the medication usage, morning VAS and evening VAS by day. Means were plotted. Daily results were compared using Wilcoxon rank sums. Multivariate analysis of variance with repeated measures was used to examine the effect of group on the medication usage, morning and evening pain levels.

Acceptance Criteria

This study is acceptable because the results show a statistical significance in pain reduction using visual analog scale (VAS).

Results

70 Patients have been enrolled to date, with 28 controls and 42 stimulator units, with 21/28 (75%) females in the control group, and 31/42 (73.8%) in the stimulated group.

Graph 1 shows the mean VAS at the start of the day while graph 2 shows the evening scores.

Repeated measures ANOVA is statistically significant for a difference in time response between the “stim” and “cont’ groups (p=0.02). The evening VAS shows no difference between groups.

Graph 3 shows medication doses for the two groups over the 7 days. There is a large clinically significant difference in usage. In the “stim” group, no medication was used on 82.3% (249/294) of the patient-days while no medication was used in the “cont” group on 68.4% (134/196) of the patient-days (p<0.001). On days 3 and 4, there was a strong trend to reduced usage by the “stim” group (p=0.07), while on day 7 the difference was larger (p=0.06). When total medication over days 1-4 is compared the “stim” group uses less than ½ that of the controls, while over the full 7 days, total medication usage drops 55%. Large variances in usage preclude significant p-values with current enrollment levels. No study related adverse events were reported by any patient.

Discussion

Plantar fasciitis is an inflammatory disorder of the foot that results in pain. The heel of the foot has a musculoskeletal structure consisting of muscles, bones, tendons, nerves and vascular components.

Using ActiPatch at night leads to a steadily increasing reduction of morning pain even though the patients use less than ½ the medication doses of the control group. The results of this study show us that ActiPatch is an extremely safe and effective treatment for plantar fasciitis. The convenience of a simple, one dose use of the device at home, provides an excellent new treatment for plantar fasciitis, especially when you compare the treatment with ActiPatch to other over the counter treatments like NSAIDs and other pain medications that have worse safety profile.