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

May 18, 2022 updated by: Biofourmis Singapore Pte Ltd.

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)

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Singapore, Singapore, 229899
        • KK Women's and Children's Hospital
      • Singapore, Singapore, 169608
        • Singapore General Hospital
      • Singapore, Singapore, 119074
        • National University Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

124 study participants, aged between 21 to 50 years old, female, who is confirmed diagnosis of endometriosis.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The concordance between Pain Index and NRS scores during the study period. (Categorised into none, mild, moderate and severe pain)
Time Frame: 12 weeks

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The correlation between 11-point Pain Index (0-10) and 11-point NRS score (0-10).
Time Frame: 12 weeks

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 12 weeks
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
Exploratory Endpoint 2: Trend of Quality of Life over the study period
Time Frame: 12 weeks
The trend of Quality of life measures will be presented using line charts.
12 weeks
Exploratory Endpoint 3: Trend of Pain Index and NRS categories over the study period
Time Frame: 12 weeks
The trend of Pain Index and NRS categories (None, Mild, Moderate, Severe) will be presented using bar graphs.
12 weeks
Exploratory Endpoint 4: Effect of concomitant medication usage on the NRS categories
Time Frame: 12 weeks
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
Exploratory Endpoint 5: Effect of concomitant medication usage on the Pain Index categories
Time Frame: 12 weeks
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
Exploratory Endpoint 6: Correlation between EQ-5D-5L and physiological parameters.
Time Frame: 12 weeks
The correlation between EQ-5D-5L and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.
12 weeks
Exploratory Endpoint 7: Correlation between EHP-30 and physiological parameters.
Time Frame: 12 weeks
The correlation between EHP-30 and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.
12 weeks
Exploratory Endpoint 8: Correlation between Productivity (HRPQ) and physiological parameters.
Time Frame: 12 weeks
The correlation between Productivity (HRPQ) and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.
12 weeks
Exploratory Endpoint 9: Correlation between PROMIS-Fatigue and physiological parameters.
Time Frame: 12 weeks
The correlation between PROMIS-Fatigue and physiological parameters will be presented as scatterplots with the Pearson correlation and statistical significance.
12 weeks
Exploratory Endpoint 10: Change in Pain Index, NRS categories over the menstrual cycle.
Time Frame: 12 weeks
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
Exploratory Endpoint 11: Change in physiological parameters over the menstrual cycle.
Time Frame: 12 weeks
Changes in physiological parameters over the menstrual cycle will be summarized using boxplots across menstrual cycle.
12 weeks
Exploratory Endpoint 12: Change in Pain Index, NRS categories by the type of lesions
Time Frame: 12 weeks
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
Exploratory Endpoint 13: Change in physiological parameters by the type of lesions
Time Frame: 12 weeks
Changes in physiological parameters over the lesion types will be summarized using boxplots across the menstrual cycle.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2020

Primary Completion (Actual)

October 28, 2021

Study Completion (Actual)

February 22, 2022

Study Registration Dates

First Submitted

December 22, 2019

First Submitted That Met QC Criteria

March 20, 2020

First Posted (Actual)

March 23, 2020

Study Record Updates

Last Update Posted (Actual)

May 19, 2022

Last Update Submitted That Met QC Criteria

May 18, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT004-AMY004JG

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

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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