Menstrual Pain

Menstrual Pain Study

 

Allay Menstrual Pain Device Treats Dysmenorhea

 

FINAL CLINICAL STUDY REPORT


Study Title: A Randomized, Clinical Study Evaluating the Safety and Efficacy of Allay Menstrual Pain Therapy in the Treatment of Primary Dysmenorrhea

Name of Device Tested: Allay Menstrual Pain Therapy

Indication: Pain and Edema Resulting from Menstruation

Sponsor: BioElectronics Corporation

Study Number: BIEL-002

Phase of Development: N/A

Study Start Date: 15 January 2009 (First Subject Enrolled)

Study End Date: 15 May 2009 (Last Subject Results Recorded)

Primary Investigators: Sheena Kong, M.D. & Barry Eppley, M.D., D.M.D.

Responsible Medical Monitor: Barry Eppley, M.D., D.M.D.

Report Date: June 2009


(This study was conducted in accordance with the guidance of Good Clinical Practice (GCP), including archiving of essential documents.)

SUMMARY OF RESULTS

Introduction

Primary Dysmenorrhea, commonly referred to as menstrual cramping, is a medical condition characterized by pain from contractions in the lower abdomen occurring at the onset of menstruation in the absence of an identifiable pelvic disease. Sharp pains in the lower abdomen begin at the start of menstruation and may continue for up to 3 or 4 days. The pain can range from mild to severe and can often interfere with many normal activities. While the majority of women who have menstrual periods experience some discomfort, an estimated 10% or more are temporarily disabled by the high level of pain that they experience. It is distinguished from secondary dysmenorrhea, which refers to painful menses resulting from pelvic pathology such as endometriosis.
Many different treatment strategies have been tried for menstrual pain but the most commonly used are non-steroidal anti-inflammatory drugs. (NSAIDS) Despite drug therapy, universal relief is not obtained and some patients experience gastric upset and other minor problems with NSAID use.
Pulsed electromagnetic field (PEMF) therapy in some form has been used or investigated since the early 1930s. There is a large body of clinical experience that has realized its value as an effective treatment for tissue trauma, particularly in the early stages of inflammation. Numerous studies are available that document its effectiveness in orthopedic surgery, arthritis, and even plastic surgery (breast augmentation, rhinoplasty, etc). While no study has demonstrated the complete elimination of pain or need for some medication relief, PEMF has shown less dependence on medications and some enhancement of the recovery period. Also, no known studies have reported adverse or harmful effects so it is fair to conclude that PEMF is safe for human use.
The precise mechanism by which PEMF works on controlling pain after injury is not known. It is theorized that it may affect pain levels by its enhancement of nitric oxide (NO) release, a short-lived signaling molecule in the anti-inflammatory cascade. It is also suggested that it has an effect on stabilizing cell membranes such that the edema phase of an injury is less or more rapidly resolved.
Allay menstrual patches have been specifically developed for application over the uterine area. The looped design functions at a frequency in the 27.1 MHz ISM band and is confined within the field of the patch’s loop antenna. The patch induces electric current in human tissue but is oscillating at such a high frequency that it cannot be detected by the patient. The high frequency results in a depth of penetration into the tissues of approximately 10 cm. When the patch is used over a 24 hour period, it produces an absorbed energy of 630mJ/cc, which is well within the range of effectiveness for soft tissue injuries. The patch produces a power density at the skin surface between 14 and 73?W/cm² and induces an electrical field of about 10 mV/cm, resulting in adsorbed power levels in the range of 7.3?W/cm3. This 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.

Results

A total of ninety-one (91) women were enrolled with moderately severe dysmenorrhea and were randomly assigned an active or control Allay Menstrual Pain Therapy device. Forty-eight (48) patients received active devices while the remaining forty-three (43) received placebo devices. The patients ranged in age from 18-34 years, with an average age of 26.2. Seventy-five percent (75%) of the subjects were White and fifteen percent (15%) of the subjects were Asian. A further breakdown is included below:

Twenty-one (23.1%) subjects discontinued prematurely. However, 95% of subjects remained in the study for Days 1 and 2 (most severe days) of their menstrual cycles. Seven percent discontinued use due to wear issues (indicated below), and five percent discontinued use because their pain was eliminated. Although the data shows that ten percent of participants indicated that they discontinued use because the device didn’t help their menstrual pain, this statistic includes the individuals given the placebo patch.

Efficacy Results

This clinical study evaluating Allay Menstrual Pain Therapy showed that 77.1% of women using the active Allay patch reported either complete elimination or reduction in their typical menstrual pain and discomfort. Within this group, 17 (35.4%) reported least a 50% reduction in pain.

Relative to the active group, in the placebo (control) group, six studies (13.95%) reported a reduction in their menstrual pain symptoms. The differences in positive response to either the active or control device was of statistical significance (p < 0.05).

Although the actual levels of pain indicated are subjective and vary by patient, the change in pain levels is the leading factor in determining efficacy. On average, pain was decreased significantly on a daily basis, as indicated in the table and charts below. The clinical results also indicate that over time the percentage of decrease in pain increases, suggesting that there is a strong correlation between duration of use of Allay and pain reduction. By Day 5, pain had been reduced by 63.2%, compared to a reduction of 31.3% on Day 1.

Although this correlation is also affected by the body’s natural tendency to reduce pain over time, the pain levels were significantly lower with use of Allay, and the rate at which pain decreased was significantly higher at the onset and end of patients’ menstrual cycles. For instance, from Day 1 to Day 2, pain decreased at a rate of 1.25x the body’s perceived normal rate of pain reduction.

The overall slopes of -0.66 and -0.86 for normal and Allay pain decrease, respectively, also suggest that pain may be reduced at a slightly faster rate overall with use of Allay, although not statistically significant.

Safety Results

One subject discontinued early from slight irritation, but there was no evidence of a clinically significant effect. No (zero) subjects experienced adverse events.

Outcome Measure Results

Satisfaction with treatment was qualitatively assessed by subject-reported patience adherence, treatment satisfaction, and symptoms questionnaire. Comments are included in Appendix A.

Conclusion

The clinical study demonstrates that the Allay Menstrual Pain Therapy is an effective and safe non-drug method for use in the treatment of primary dysmenorrhea. Allay can be offered as a primary, drug-free treatment method for women suffering from moderate dysmenorrhea. In more severe cases of dysmenorrhea, it can be an adjuvant treatment to reduce the duration of use or the amount of other oral medications.


Appendix A.

Primary Investigators

Dr. Sheena Kong is a Board Certified Internist. Dr. Kong received a Doctor of Medicine Degree from Washington University, St. Louis. She completed her residency in internal medicine at California Pacific Medical Center in San Francisco. Prior to medical school, she studied at Harvard University, where she graduated with a Master’s Degree in Medical Sciences. Dr. Kong has an active internal medicine private practice in San Francisco, California and is part of San Francisco Internal Medicine Associates.

Sheena Kong, M.D.
1199 Bush St

San Francisco, CA 94109

415-267-8740

Barry L Eppley, MD, DMD is a highly-skilled plastic surgeon and the only plastic surgeon in the Midwest certified by both the American Board of Plastic Surgery and the American Board of Oral and Maxillofacial Surgery. Dr. Eppley has prominent international experience in the investigation and development of numerous technologic advances in medicine and plastic surgery. He has been the recipient of numerous National Institute of Health and private corporate research grants and studies for the evaluation of promising surgical technologies and medical implants. As a result, he has been awarded numerous U.S. and international patents on biomedical technologies. Dr. Eppley completed in 2009 the National Institutes of Health (NIH) Office of Extramural Research web-based training course “Protecting Human Research Participants” (Certificate Number: 227968).

Barry L. Eppley, M.D., D.M.D.
1111 North Ronald Reagan Parkway
Avon, Indiana 46123

317-06-5167

Ethics

The proposed study and the device design were reviewed by Drs. Barry Eppley, M.D. (Indianapolis, IN), Sheena Kong, M.D. (San Francisco,CA), Joe Danyo, M.D. (Wilmington, DE) and Lee Corbett, M.D. (Louisville, KY). It was collectively determined that the device posed no risk of any adverse human effects nor should its use interfere with any normal bodily functions. The study design was approved as a non-invasive treatment protocol with survey assessment that would not expose any study subjects to harm or increased exposure to pain.

Design

A prospective double-blinded clinical study was conducted in two different cities (Indianapolis and San Francisco) of randomly selected women from the investigator’s medical practices, ages 18 to 35. Allay patches were asked to be worn at the onset of one’s menstrual cycle and worn for five consecutive days if possible. The outcome measure was a visual analog scale for each patient’s assessment of her menstrual pain severity wearing the patch versus that compared to their perception of their traditional cycle pain. The means of each group was statistically analyzed by a paired difference t-test.

  • The study is a prospective randomized double-blind, placebo- and positive-controlled trial of PEMF versus placebo in adult women for primary dysmenorrhea.
  • Participation is voluntary and subjects can withdraw at any time.
  • Greater than 75 patients: at least 30 control and 30 active patients.
  • One menstrual cycle study period.
  • Age range of 18 to 35 who have menstrual cycles that they consider significant and disabling. Women with secondary dysmenorrhea are specifically excluded.
  • Control patches will be identical as the actives but will not have a live battery. This will be unknown to either the study subjects or the investigators.
  • Patients will wear the patch inside their underwear for 24 hours per day for up to five days at the first sign of menstrual discomfort.
  • Patients will be given a Pain Recording Visual Analog Scale sheet to record their perceived level of pain experienced over their menstrual period as well as a section to make comments at study completion.
  • Patients are to take, if needed, any medications that they might normally take for pain relief during a normal menstrual cycle.
  • The primary outcome measure is to determine if there is a difference in pain reduction in the active vs. placebo study groups.
  • The secondary outcome measure is to determine the significance of the placebo effect between the active vs. placebo study groups.
  • The null hypothesis is that no difference exists in pain reduction between the active and the placebo study groups. (i.e., the mean pain rating scores between the same groups is the same)
  • The alternative hypothesis is that the active study group will show a lower overall pain score than the placebo group.

Commentaries

Effectiveness

  • ‘I can honestly say that I don’t know if the device made me feel better or it was a psychological effect of it, but there was definitely a decrease in pain’
  • ‘I was surprised how fast I forgot I was wearing it’
  • ‘I still got the stabbing pain while wearing the device, although it wasn’t as bad’
  • ‘This product was very useful to heal my menstrual pain especially during the first day of my period. This is a better way to kill the pain than using Tylenol or other pills.’
  • ‘…I swear I felt some warmth…and my normal period pain was much less severe!’
  • ‘This was awesome! Absolutely no pain during the first and second days which are usually the worst.’
  • ‘I feel this product provided local analgesia, similar to Tylenol. I placed the product on other parts of my body where I had aches and pain…and it seemed to relieve the pains there too.’

Wear Issues

  • ‘….very uncomfortable. It became warm and I started to sweat…which made me not use it anymore…’
  • ‘…if you make it smaller, people would be more inclined to use it.’
  • ‘A little awkward to wear with clothing.’
  • ‘…fell out on the floor when using the bathroom.’
  • ‘..it should come with something like straps or tapes to hold it into place.’

Discussion

Menstrual cramps and pain are the result of contractions of the uterus. Prostaglandins stimulate the uterine muscles to contract and shed its lining. Women who have high levels of prostaglandins will experience more intense contractions of their uterus and subsequently more pain. The benefit of anti-inflammatory medications is directed towards modulating one’s responsiveness to prostaglandin levels. Unfortunately, anti-inflammatory medications are not always completely effective at relieving menstrual pain and they have well-known side effects as well. A non-drug alternative would be a novel approach to the treatment of menstrual pain and would address a significant unmet need.

This clinical study has demonstrated that the Allay menstrual patch is effective at reducing and/or ameliorating the pain from dysmenorrhea. It is statistically significant that the active patch group exhibited a 77% positive response compared to just a 9% positive response in the placebo. It does so with no reported side effects other than some wear issues undoubtedly related to the design or material issues of the patch.

The exact mechanism by which the PEMF of the Allay patch works for menstrual pain is currently speculative. Certainly, the placebo enhancement effect plays a role but that alone cannot exclusively account for the study results, particularly in the face of such a discrepant and very low positive response to the control group patches. Modulation of pain pathways is one potential explanation Pain signals are transmitted along nerve cells to pre-synaptic terminals. PEMF has been shown to result in pre-synaptic terminals that have slowed release of neurotransmitters by altering membrane potentials thus blocking or reducing pain signals. Another potential mechanism is the well-known anti-inflammatory PEMF by affecting T-cell activity and inflammatory mediator releases. It is likely that the cumulative effect of all of these three different mechanisms accounts for the positive responses seen.

PEMF therapy appears to have a role in the management of pain from dysmenorrhea which is currently dominated by pharmaceutical and some surgical treatments. PEMF offers a noninvasive approach with no side effects and no potential for drug interactions.