Clinical trial NCT04318275: Objective Pain Measurement Using a Wearable Biosensor and a Mobile Platform in Patients With Endometriosis
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)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Endometriosis
Lead sponsor: Biofourmis Singapore Pte Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2020-03-23
Enrollment: 90
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 124 study participants, aged between 21 to 50 years old, female, who is confirmed diagnosis of endometriosis.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The concordance between Pain Index and NRS scores during the study period. (Categorised into none, mild, moderate and severe pain)
timeFrame: 12 weeks
Secondary outcomes:
measure: The correlation between 11-point Pain Index (0-10) and 11-point NRS score (0-10).
timeFrame: 12 weeks
Other outcomes:
measure: 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.
timeFrame: 12 weeks
measure: Exploratory Endpoint 2: Trend of Quality of Life over the study period
timeFrame: 12 weeks
measure: Exploratory Endpoint 3: Trend of Pain Index and NRS categories over the study period
timeFrame: 12 weeks
measure: Exploratory Endpoint 4: Effect of concomitant medication usage on the NRS categories
timeFrame: 12 weeks
measure: Exploratory Endpoint 5: Effect of concomitant medication usage on the Pain Index categories
timeFrame: 12 weeks
measure: Exploratory Endpoint 6: Correlation between EQ-5D-5L and physiological parameters.
timeFrame: 12 weeks
measure: Exploratory Endpoint 7: Correlation between EHP-30 and physiological parameters.
timeFrame: 12 weeks
measure: Exploratory Endpoint 8: Correlation between Productivity (HRPQ) and physiological parameters.
timeFrame: 12 weeks
measure: Exploratory Endpoint 9: Correlation between PROMIS-Fatigue and physiological parameters.
timeFrame: 12 weeks
measure: Exploratory Endpoint 10: Change in Pain Index, NRS categories over the menstrual cycle.
timeFrame: 12 weeks
measure: Exploratory Endpoint 11: Change in physiological parameters over the menstrual cycle.
timeFrame: 12 weeks
measure: Exploratory Endpoint 12: Change in Pain Index, NRS categories by the type of lesions
timeFrame: 12 weeks
measure: Exploratory Endpoint 13: Change in physiological parameters by the type of lesions
timeFrame: 12 weeks
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Biofourmis Inc.
name: Maulik Majmudar, M.D.
role: STUDY_CHAIR
References:
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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.
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