Objective Pain Measurement Using a Wearable Biosensor and a Mobile Platform in Patients With Endometriosis

Endometriosis Clinical Trial

— OPINE  

Official title:

An Early Feasibility Study to Explore a Novel Objective Pain Measurement Using a Wearable Biosensor and a Novel Mobile Platform in Patients With Endometriosis (OPINE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04318275
• Other study ID #: CT004-AMY004JG
• Status: Completed
• Start date: November 6, 2020
• Est. completion date: February 22, 2022

Study information

• Verified date: May 2022
• Source: Biofourmis Singapore Pte Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to explore a novel objective measurement for endometriosis-related pain. A variety of pain symptoms are associated with endometriosis, including dysmenorrhea, dyspareunia, dysuria, dyschezia and chronic pelvic pain. However, a clear characterization of pain typology and topology in populations with endometriosis, other gynecologic pathology, or a normal pelvis is lacking. Understanding the precise nature of the relationship between pain and endometriosis is important for the clinical management of affected women, given the body of evidence indicating that medical and surgical management for pain associated with endometriosis has been shown to be effective. Evaluating the relationship between pain and endometriosis, however, is challenging given that pain is difficult to measure and the mechanism by which endometriosis causes pain is not well understood. While previous studies have provided important data on the incidence of pelvic pain and endometriosis, little research has been done to assess both the typology and topology of pelvic pain, pain beyond the pelvis, endometriosis diagnosis, or severity of pain using operative findings and a standardized classification system.

Description:

BACKGROUND ON ENDOMETRIOSIS

A variety of pain symptoms are associated with endometriosis, including dysmenorrhea, dyspareunia, dysuria, dyschezia and chronic pelvic pain. However, a clear characterization of pain typology and topology in populations with endometriosis, other gynecologic pathology, or a normal pelvis is lacking. Understanding the precise nature of the relationship between pain and endometriosis is important for the clinical management of affected women, given the body of evidence indicating that medical and surgical management for pain associated with endometriosis has been shown to be effective. Evaluating the relationship between pain and endometriosis, however, is challenging given that pain is difficult to measure and the mechanism by which endometriosis causes pain is not well understood. While previous studies have provided important data on the incidence of pelvic pain and endometriosis, little research has been done to assess both the typology and topology of pelvic pain, and pain beyond the pelvis, and endometriosis diagnosis and severity using operative findings and a standardized classification system.

Historically, pain has been measured using subjective scales to determine the presence of pain and its severity. Common scales include the numeric rating scale (NRS), visual analog scale (VAS), and visual response scale (VRS). While this is important information, self-reporting is a problematic metric for both diagnostic and research purposes as it depends on pain history, cognitive and behavioral factors, and can vary over time. Other measures used in clinical practice, such as the Biberoglu and Behrman (B&B) score, incorporate both patient and clinician assessments of pain. However, patients describe symptomatology and gynecologists evaluate tenderness and induration during physical examination with an exceedingly high risk of bias and inconsistent reproducibility. Over the past few years, significant advances have been made in the development of valid biomarkers or surrogate markers for the presence and severity of pain. Measurement of various physiology parameters like heart rate, heart rate variability and electrodermal activity have shown to be associated with the presence of pain and can aid clinical interpretation.

STUDY RATIONALE

Several ratings, such as the numeric rating scale (NRS) are mainly used in clinical trials to determine the presence and severity of pain associated with endometriosis. Patient Reported Outcomes (PRO) such as NRS can be problematic as they are subjective, containing recall bias, and can vary over time. Thus, a more accurate and objective measurement of pain is needed to evaluate the efficacy of treatment with pain associated with endometriosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: February 22, 2022
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years to 50 Years

Eligibility

Inclusion criteria:

1. Able to give a written Informed Consent Form.

2. Patient who is willing to comply with study restrictions including E4® device management (wearing and charging the device) and Femme Rhythm Patient App Management (pairing E4® device and the patient Femme Rhythm App, and carrying the smartphone for answering questionnaires and data reporting)

3. Female patients aged = 21 and < 50 years.

4. Patient who meets either A or B or both in the following criteria: A. Confirmed diagnosis of endometriosis (laparoscopy/laparotomy) performed WITHIN 10 YEARS prior to the study participation.

B. Current clinical diagnosis (endometriotic cysts or deep infiltrating endometriosis detected by TVUS, TRUS or MRI) WITHIN 6 MONTHS prior to the study participation.

5. Patient who meets either A or B in the following criteria:

A. Patient is NOT treated with hormonal agents for endometriosis WITHIN 4 WEEKS prior to study participation, and have regular menses (i.e. 21-38 days) within 38 days prior to the study participation.

B. Patient started hormonal agents for endometriosis, including combined oral contraceptives MORE THAN 8 WEEKS prior to the study participation, or progestins, danazol, GnRH agonists, GnRH antagonists or Progesterone and Levonorgestrel Releasing IUDs MORE THAN 12 WEEKS prior to the study participation, AND stable use of the medication is expected during the study period

6. Patient has a moderate to severe endometriosis- associated pelvic pain using the Monthly Assessment of Endometriosis Pain within 28 days prior to study participation

Exclusion criteria:

1. Patient is pregnant, or breast feeding or is planning a pregnancy during participation of the study or is less than 6 months postpartum, post-abortion, or post-pregnancy before participation.

2. Patient has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain (e.g., pelvic inflammatory disease).

3. Patient has more than five surgical histories in pelvic area.

4. Patient has a skin disease or condition that would interfere with the collection or interpretation of physiological data obtained through E4®

5. Patient required neuromodulator (a long-acting or immediate release narcotic, or gabapentin) during 3 months prior to the study participation.

6. Patient has a planned surgery during the study.

7. Patient had a surgery within 4 weeks prior to the study participation.

8. Patient has a planned trip overseas during the study participation.

9. Any other reason that, in the judgment of the investigator, would render the subject unsuitable for the study participation.

Related Conditions & MeSH terms

• Endometriosis

Locations

Country	Name	City	State
Singapore	KK Women's and Children's Hospital	Singapore
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Biofourmis Singapore Pte Ltd.	Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Singapore,  Taiwan, 

References & Publications (13)

Ballard K, Lane H, Hudelist G, Banerjee S, Wright J. Can specific pain symptoms help in the diagnosis of endometriosis? A cohort study of women with chronic pelvic pain. Fertil Steril. 2010 Jun;94(1):20-7. doi: 10.1016/j.fertnstert.2009.01.164. Epub 2009 Apr 1. — View Citation

Ballard KD, Seaman HE, de Vries CS, Wright JT. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study--Part 1. BJOG. 2008 Oct;115(11):1382-91. doi: 10.1111/j.1471-0528.2008.01878.x. Epub 2008 Aug 19. — View Citation

Bourdel N, Alves J, Pickering G, Ramilo I, Roman H, Canis M. Systematic review of endometriosis pain assessment: how to choose a scale? Hum Reprod Update. 2015 Jan-Feb;21(1):136-52. doi: 10.1093/humupd/dmu046. Epub 2014 Sep 1. Review. — View Citation

Cox L, Ayers S, Nala K, Penny J. Chronic pelvic pain and quality of life after laparoscopy. Eur J Obstet Gynecol Reprod Biol. 2007 Jun;132(2):214-9. Epub 2006 May 30. — View Citation

Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005 Nov-Dec;11(6):595-606. Epub 2005 Sep 19. Review. — View Citation

Hsu AL, Sinaii N, Segars J, Nieman LK, Stratton P. Relating pelvic pain location to surgical findings of endometriosis. Obstet Gynecol. 2011 Aug;118(2 Pt 1):223-230. doi: 10.1097/AOG.0b013e318223fed0. — View Citation

Kang SB, Chung HH, Lee HP, Lee JY, Chang YS. Impact of diagnostic laparoscopy on the management of chronic pelvic pain. Surg Endosc. 2007 Jun;21(6):916-9. Epub 2006 Nov 14. — View Citation

Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014 Apr;101(4):927-35. doi: 10.1016/j.fertnstert.2014.02.012. Epub 2014 Mar 13. Erratum in: Fertil Steril. 2015 Aug;104(2):498. — View Citation

Renner SP, Boosz AS, Burghaus S, Maihöfner C, Beckmann MW, Fasching PA, Jud SM. Visual pain mapping in endometriosis. Arch Gynecol Obstet. 2012 Sep;286(3):687-93. doi: 10.1007/s00404-012-2369-4. Epub 2012 May 9. — View Citation

Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997 May;67(5):817-21. — View Citation

Rotondi MA, Donner A. A confidence interval approach to sample size estimation for interobserver agreement studies with multiple raters and outcomes. J Clin Epidemiol. 2012 Jul;65(7):778-84. doi: 10.1016/j.jclinepi.2011.10.019. Epub 2012 May 4. — View Citation

Schliep KC, Mumford SL, Peterson CM, Chen Z, Johnstone EB, Sharp HT, Stanford JB, Hammoud AO, Sun L, Buck Louis GM. Pain typology and incident endometriosis. Hum Reprod. 2015 Oct;30(10):2427-38. doi: 10.1093/humrep/dev147. Epub 2015 Aug 11. — View Citation

Yong PJ, Williams C, Bodmer-Roy S, Ezeigwe C, Zhu S, Arion K, Ambacher K, Yosef A, Wong F, Noga H, Britnell S, Yager H, Bedaiwy MA, Brotto LA, Albert AY, Lisonkova S, Allaire C. Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting. J Sex Med. 2018 Dec;15(12):1765-1775. doi: 10.1016/j.jsxm.2018.10.005. Epub 2018 Nov 13. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Endpoint 1: Correlation between Quality of Life (EQ-5D-5L and EHP-30), Productivity (HRPQ), PROMIS-Fatigue with Sleep Quality and Stress Values calculated using Biofourmis's propriety algorithm.	The Pearson correlation and its statistical significance between the various Quality of Life measures and the Sleep Quality and Stress Values (calculated using Biofourmis's propriety algorithm) will be presented in a matrix table.	12 weeks
Other	Exploratory Endpoint 2: Trend of Quality of Life over the study period	The trend of Quality of life measures will be presented using line charts.	12 weeks
Other	Exploratory Endpoint 3: Trend of Pain Index and NRS categories over the study period	The trend of Pain Index and NRS categories (None, Mild, Moderate, Severe) will be presented using bar graphs.	12 weeks
Other	Exploratory Endpoint 4: Effect of concomitant medication usage on the NRS categories	Effects of concomitant medication usage will be measured as an increment or decrement in NRS pain categories (None, Mild, Moderate, Severe), based on the highest pain reported by patient before taking the medication and the pain report after medication usage.	12 weeks
Other	Exploratory Endpoint 5: Effect of concomitant medication usage on the Pain Index categories	Effects of concomitant medication usage will be measured as an increment or decrement in Pain Index categories (None, Mild, Moderate, Severe), based on the highest pain reported by patient before taking the medication and the Pain Index generated based on the pain report after medication usage.	12 weeks
Other	Exploratory Endpoint 6: Correlation between EQ-5D-5L and physiological parameters.	The correlation between EQ-5D-5L and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.	12 weeks
Other	Exploratory Endpoint 7: Correlation between EHP-30 and physiological parameters.	The correlation between EHP-30 and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.	12 weeks
Other	Exploratory Endpoint 8: Correlation between Productivity (HRPQ) and physiological parameters.	The correlation between Productivity (HRPQ) and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.	12 weeks
Other	Exploratory Endpoint 9: Correlation between PROMIS-Fatigue and physiological parameters.	The correlation between PROMIS-Fatigue and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.	12 weeks
Other	Exploratory Endpoint 10: Change in Pain Index, NRS categories over the menstrual cycle.	Changes in Pain Index, NRS categories (None, Mild, Moderate, Severe) over the menstrual cycle will be summarized by plotting bar graphs across menstrual cycle.	12 weeks
Other	Exploratory Endpoint 11: Change in physiological parameters over the menstrual cycle.	Changes in physiological parameters over the menstrual cycle will be summarized using boxplots across menstrual cycle.	12 weeks
Other	Exploratory Endpoint 12: Change in Pain Index, NRS categories by the type of lesions	Changes in Pain Index, NRS categories (None, Mild, Moderate, Severe) over the lesion types will be summarized using bar graphs across the menstrual cycle.	12 weeks
Other	Exploratory Endpoint 13: Change in physiological parameters by the type of lesions	Changes in physiological parameters over the lesion types will be summarized using boxplots across the menstrual cycle.	12 weeks
Primary	The concordance between Pain Index and NRS scores during the study period. (Categorised into none, mild, moderate and severe pain)	Pain Index will be generated via vital sign collected from subjects and processed by Biofourmis's propriety algorithm. Both pain index and NRS will be categorised into None (0), Mild (1-3), Moderate (4-6), and Severe (7-10) pain.; Concordance will be measured using unweighted Kappa Statistic for multiple categories with 95% CI. Percentage agreement between the categories will be also calculated by taking the number of concordant pairs divided by the total number of pain episodes.	12 weeks
Secondary	The correlation between 11-point Pain Index (0-10) and 11-point NRS score (0-10).	The generated Pain Index will be classified into 11 points (0-10) in accordance with the raw NRS score.; Correlation between the 11-point Pain Index and raw NRS score will be measured using Spearman correlation.	12 weeks