The Developmental Origins of Endometriosis (ENDOHaD)
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| ClinicalTrials.gov Identifier: NCT05951452 |
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Recruitment Status :
Recruiting
First Posted : July 19, 2023
Last Update Posted : May 3, 2024
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Introduction:
Endometriosis is a common pathology affecting one in 10 women, characterized by the ectopic development of endometrium, which can cause pain and/or infertility. This pathology is primarily determined by hereditary factors, but it is also susceptible to environmental influences, such as the age of the onset of menstruation or exposure to chemical substances that modify the endocrine system. Recent studies have highlighted that endometriosis is more common in women with relatively short ano-genital distances (AGD), and that sensitivity to pain is closely linked to adult levels of testosterone (T) or oxytocin (OT).
Aim:
The main objective is to compare the anogenital distance (AGD) between two groups of women: one with stage III or IV endometriosis (ENDO +) and another group without endometriosis confirmed by laparoscopy (ENDO -).
The secondary objectives are to compare various factors between the 2 groups :
- Basal testosterone levels in blood.
- Variations in blood testosterone levels before and after a video stimulating empathy.
- Basal oxytocin levels in saliva.
- Variations in oxytocin levels in saliva before and after an empathy-stimulating video.
- Pelvic pain, between D2 and D5 after the start of the menstrual cycle.
For the ENDO + group only:
- Evaluate patients' quality of life, between D2 and D5 after the start of the menstrual cycle.
- Correlate pain experienced over the last 4 weeks with hormonal markers (AGD, T, OT).
Methods:
Participants in the ENDO+ group will fill in a questionnaire assessing the impact of pain experienced over the past 4 weeks on their quality of life. D0 is defined as the day when participants experience a menstrual bleed before 10 am. All participants will return for project-specific hospital appointment between D2 and D5 after the start of their menstrual cycle to measure T, Sex Hormone-Binding Globulin (SHBG) and OT.
During this consultation, the following samples will be taken:
- 10mL blood sample
- 2mL saliva sample
Both samples will be taken at t0 (before watching the video) and t1 (20 minutes after watching the video).
| Condition or disease | Intervention/treatment |
|---|---|
| Endometriosis | Other: Blood samples for testosterone and SHBG measurements Other: Saliva samples for oxytocin measurements |
| Study Type : | Observational |
| Estimated Enrollment : | 40 participants |
| Observational Model: | Case-Control |
| Time Perspective: | Prospective |
| Official Title: | The Developmental Origins of Endometriosis |
| Actual Study Start Date : | January 8, 2024 |
| Estimated Primary Completion Date : | December 1, 2026 |
| Estimated Study Completion Date : | December 1, 2026 |
| Group/Cohort | Intervention/treatment |
|---|---|
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ENDO +
Patients with endometriosis diagnosed by Magnetic Resonance Imaging (MRI) or laparoscopy
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Other: Blood samples for testosterone and SHBG measurements
Several measurements of the testosterone concentration will be performed on serum from 10 mL of blood collected at:
Other: Saliva samples for oxytocin measurements Several measurements of the oxytocin concentration will be performed on 2 ml saliva samples:
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ENDO -
Patients without endometriosis diagnosed by laparoscopy
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Other: Blood samples for testosterone and SHBG measurements
Several measurements of the testosterone concentration will be performed on serum from 10 mL of blood collected at:
Other: Saliva samples for oxytocin measurements Several measurements of the oxytocin concentration will be performed on 2 ml saliva samples:
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- Measure of the anogenital distance (AGD) [ Time Frame: At diagnosis or at inclusion ]
AGD is measured at enrollment for patients already diagnosed by Magnetic resonance imaging (MRI), and it is measured during the laparoscopy once the diagnosis has been confirmed.
AGD is measured by 2 different operators with a millimetric precision ruler according 2 validated methods :
- measure of the distance from the clitoral surface to the anus (AGD-AC), and
- measure of the distance from the posterior fourchette to the anus (AGD-AF). The method is described here: https://www.jove.com/v/57912/ Each operator will measure the AGD-AC and the AGD-AF 3 times. For each type of AGD, the final value will correspond to the mean of the 6 values.
- Basal total testosterone [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video ]The basal total testosterone (Ttotal(t0)) level is measured in blood
- Basal bio-available testosterone [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video ]The basal bio-available testosterone (Tbio-available(t0)) level is measured in blood
- Basal sex hormone-binding globulin [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video ]Basal sex hormone-binding globulin (SHBG(t0)) level is mesured in blood
- Basal Free Androgen Index [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video ]Basal Free Androgen Index (FAI(t0)) = (Ttotal(t0)/SHBG(t0))*100
- Total testosterone after empathy induction [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]The total testosterone level after empathy induction (Ttotal(t1)) is measured in blood
- Bio-available testosterone after empathy induction [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]The bio-available testosterone level after empathy induction (Tbio-available(t1)) is measured in blood
- Sex hormone-binding globulin after empathy induction [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]Sex hormone-binding globulin after empathy induction (SHBG(t1)) is mesured in blood
- Free Androgen Index after empathy induction [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]Free Androgen Index after empathy induction (FAI(t1)) = (Ttotal(t1)/SHBG(t1))*100
- Variation in total testosterone levels before and after an empathy-inducing video [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]The level of variation in total testosterone before (t0) and after watching empathy-inducing video (t1) is assessed according to: Ttotal(t1)-Ttotal(t0)
- Variation in bio-available testosterone levels before and after an empathy-inducing video [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]The level of variation in bio-available testosterone before (t0) and after watching empathy-inducing video (t1) is assessed according to: Tbio-available(t1)-Tbio-available(t0)
- Variation in Sex hormone-binding globulin levels before and after an empathy-inducing video [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]The level of variation in Sex hormone-binding globulin before (t0) and after watching empathy-inducing video (t1) is assessed according to: SHBG(t1)-SHBG(t0)
- % of variation in Free Androgen Index before and after an empathy-inducing video [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]% of variation in Free Androgen Index before (t0) and after watching empathy-inducing video (t1) is assessed according to: [[FAI(t1)-FAI(t0)]/FAI(t0)] × 100
- Basal oxytocin (OT) level [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video ]
The basal OT level is measured by the dosage in the saliva of :
Total OT (OTtotal(t0))
- Oxytocin (OT) level after empathy induction [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video ]
The basal OT level is measured by the dosage in the saliva of :
Total OT (OTtotal(t1))
- Variation in oxytocin (OT) level before and after an empathy-inducing video [ Time Frame: t1 : Between the second and the fifth day of the menstrual cycle, after wathching empathy-inducing video ]
Variation in OT level before (t0) and after watching an empathy-inducing video (t1) is assessed in the saliva according to:
- OTtotal(t1)-OTtotal(t0)
-% of variation of OT = [[OT(t1)-OT(t0)]/OT(t0)] × 100
- Area under the Receiving Operator Characteristic (ROC) curve for AGD [ Time Frame: At diagnosis (ENDO+) or at enrollment (ENDO-) ]
The ROC curve is a graphical representation that illustrates the performance of a binary classification model. It plots the true positive rate (sensitivity) against the false positive rate (1 - specificity) at various classification thresholds. In other words, the model's sensitivity corresponds to the model's ability to detect patients (ENDO+) while the model's specificity corresponds to the model's ability to detect a non-patient (ENDO-). The ROC curve helps assess the model's ability to correctly identify true positives while minimizing false positives.
The area under the ROC curve (AUC) can be interpreted as the probability that, among two randomly chosen subjects, a patient and a non-patient, the value of the marker is higher for the patient than for the non-sick. An AUC of 0.5 (50%) indicates that the marker is non-informative. An increase in AUC indicates an improvement in discriminatory abilities, with a maximum of 1.0 (100%).
- Pelvic pain intensity [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video ]Pelvic pain will be assessed using a Visual Analogue Scale (VAS). The visual analog scale (VAS) is a validated, unidimensional subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain."
- Quality of life (for the ENDO+ group only) [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video ]
The quality of life of patients with endometriosis is assessed with the Endometriosis Health Profile questionnaire (EHP-30©)
EHP-30 is a self-administered questionnaire validated in French to assess the effects that endometriosis can have on the quality of life of women. This questionnaire consists of 30 domains grouped into 5 areas:
Pain (11 items: n° 1 to 11), Control and helplessness (6 items: n°12 to 17), Emotional well-being (6 items: n°18 to 23), Social support (4 items: n°24 to 27), Self-image (3 items: n°28 to 30). Each item is rated on a Likert scale (Never=0, Rarely=1, Sometimes=2, Often=3, Always=4). Each domain is then represented by a score calculated on a scale from 0 (indicating the best possible state of health) to 100 (indicating the worst possible state of health): Domain score = [sum of responses to each item in the domain] / [4 (= maximum item response) × number domain items] × 100
- Score of pain (for the ENDO+ group only) [ Time Frame: t0 : Between the second and the fifth day of the menstrual cycle, before wathching empathy-inducing video ]The score of pain of patients with endometriosis is assessed with the French version of the Endometriosis Health Profile questionnaire (EHP-30©). The score of the first domain Pain consists of 11 items. Each item is rated on a Likert scale (Never=0, Rarely=1, Sometimes=2, Often=3, Always=4).
Biospecimen Retention: Samples Without DNA
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| Ages Eligible for Study: | 20 Years to 38 Years (Adult) |
| Sexes Eligible for Study: | Female |
| Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Nulliparous woman
- No hormonal contraception for at least 3 months
- Regular menstrual cycles (between 26 and 32 days) or proven ovulation (positive urine ovulation test ovulation test or progesterone level >3 ng/ml in the luteal phase)
- Normal BMI (≥ 18,5 and < 30 kg/m²)
Specific criteria (ENDO+ group) :
- Stage III or IV endometriosis confirmed by laparoscopy or by laparotomy or MRI
- Painful symptoms
Specific criteria (ENDO- group) :
• Patient without endometriosis confirmed by laparoscopy
Exclusion Criteria:
- Ovarian stimulation planned within 3 months
- Adenomyosis
- Use of a copper coil
- Polycystic ovary syndrome
- Pudendal neuralgia
- Episiotomy or lesion of the posterior perineum that may modify AGD
- Diabetes or thyroid disease
- Chronic liver failure, chronic renal failure, cardiac pathology, autoimmune disease
- Autism
- Diagnosis and/or treatment for psychiatric illness
- Chronic exposure to cocaine, methamphetamine, morphine or ecstasy within 30 days before the inclusion visit
- Chronic exposure to Tetrahydrocannabinol (THC) within 7 days prior to inclusion.
- Patient on treatment(s) that vary oxytocin (e.g. atosiban), testosterone or GnRH
- Pregnant or breast-feeding patient
- Patients who have given birth or breastfed within 6 weeks before the inclusion visit
- Patient unable to read French
- Failure to obtain informed consent
- Patient not affiliated with or not benefiting from a national health insurance scheme
- Person under legal protection, guardianship or curatorship
- Patient participating in other research involving the human person
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05951452
| Contact: Alexandra ALVERGNE, PhD | +334.67.14.46.15 | alexandra.alvergne@umontpellier.fr | |
| Contact: Noémie RANISAVLJEVIC, MD | +334.67.33.64.81 | n-ranisavjlevic@chu-montpellier.fr |
| France | |
| CHU de Montpellier | Recruiting |
| Montpellier, France, 34295 | |
| Contact: Noémie RANISAVLJEVIC, MD n-ranisavljevic@chu-montpellier.fr | |
| Principal Investigator: Noémie RANISAVLJEVIC, MD | |
| Sub-Investigator: Martha DURAES, MD | |
| Study Chair: | Alexandra ALVERGNE, PhD | Centre National de la Recherche Scientifique, France |
| Responsible Party: | University Hospital, Montpellier |
| ClinicalTrials.gov Identifier: | NCT05951452 |
| Other Study ID Numbers: |
RECHMPL23_0057 |
| First Posted: | July 19, 2023 Key Record Dates |
| Last Update Posted: | May 3, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Endometriosis Testosterone Oxytocin DOHaD |
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Endometriosis Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Diseases Oxytocin |
Testosterone Oxytocics Reproductive Control Agents Physiological Effects of Drugs Androgens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |