The Effect of Selective Oxytocin Receptor Inhibitors on Endometriosis-related Pain (ENDOBAN)

A pilot study to investigate the potential role of atosiban, a selective oxytocin receptor inhibitor, in the management of endometriosis-related pain. Ten patients will be administered atosiban intravenously during 6 hours on a day during their period when they experience (severe) pain

Study Overview

• Status: Recruiting
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Atosiban

Detailed Description

Rationale: Endometriosis is a common chronic, incurable condition in which endometrium-like tissue implants outside the uterus. In the Netherlands approximately 405,000 women between 15 and 50 years of age are estimated to have endometriosis in some degree. Symptoms may vary through the menstrual cycle and include but are not limited to: dysmenorrhea (pain during menstruation), chronic pelvic pain, dyspareunia (pain during or after sexual intercourse) and dyschezia (pain during defecation). Current treatment options consist of analgesics, hormonal treatment and more or less invasive surgery. Following histological findings and in vitro and animal research, oxytocin receptor antagonists might be an alternative, non-hormonal, non-invasive treatment option. Except for one study on advanced reproductive techniques, no studies have reported the use of selective oxytocin receptor antagonists in human patients. The investigators hypothesize atosiban, a selective oxytocin receptor antagonist that is currently available in an intravenous administration form, can significantly lower patients' pain scores. If this pilot study shows atosiban is an effective treatment option for women with endometriosis, the investigators intend to develop a patient-friendly mode of administration for atosiban.

Objective: To investigate the potential of atosiban as a treatment for pain caused by endometriosis.

Study design: Phase II interventional pilot study Study population: 10 patients with laparoscopic, MRI or ultrasound proven endometriosis Intervention (if applicable): Atosiban 6,75mg intravenously bolus, followed by 18mg per hour continuous infusion for 3 hours, followed by 6mg per hour continuous infusion for 3 more hours.

Main study parameters/endpoints: Reduction in pain score (VAS), use of analgesics, experienced side effects.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will be admitted in day-care while they will receive intravenous treatment with atosiban. They will be asked to keep a menstrual diary for one month, one time before the treatment and another time afterwards. Furthermore, participants will be asked to fill in questionnaires on quality of life and their medical history. Their pain scores will be taken at several time points. The investigators will take blood samples at the start and at the end of the treatment. The most important risk for participants is the risk of side effects related to atosiban. These include nausea (>10%), headache, dizziness, flushes, tachycardia, hypotension, vomiting, hypoglycaemia and local reaction on the place of injection (1-10%). The most severe side effect described is pulmonary oedema. This was mostly in combination with other tocolytic agents and very rare, the side effects are generally considered to be mild. Atosiban has been administered on a routine basis to pregnant women with preterm labour in the same regimen as is used now. However, the investigators will administer atosiban for a shorter period of time. According to the risk classification of the Netherlands Federation of University hospitals for patients participating in this study, the risk has been assessed as "moderate".

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud University Medical Center
    • Contact: Theodoor E Nieboer, MD, PhD; Phone Number: 0031243614788; Email: bertho.nieboer@radboudumc.nl
    • Contact: Mark E Schoep, MD; Email: mark.schoep@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Laparoscopic, MRI or ultrasound confirmed endometriosis
• Dysmenorrhea with an average pain score ≥5 on the most painful day during menstrual period or withdrawal bleeding

Exclusion Criteria:

• Inability to come to the hospital for the experiment
• Suspicion on a (post)menopausal state
• Continuous treatment with oral contraceptives or progestagens
• Current use of gonadotrophin releasing-hormone agonist
• Current ovarian stimulation
• Current breastfeeding
• Labour or breastfeeding within the last 6 weeks
• Diagnosis of chronic pelvic pain
• Inability to give informed consent
• Language barrier
• Diabetes Mellitus, type I or II
• Hypersensitivity to atosiban or mannitol
• Use of systemic betamimetics
• Use of calcium channel blockers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention; All the participants in this pilot study will receive atosiban	Drug: Atosiban; Pilot study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in pain during and after the administration of atosiban	Pain scores on a visual analogue scale from 0 to 10, where higher scores mean more pain, during treatment and the month following treatment	Change from baseline up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of atosiban	Side effects may include headache, nausea and dizziness. Side effects are measured on visual analogue scale from 0 to 10, where higher scores mean more complaints.	Up to 4 weeks
Levels of serum prostaglandins	Prostaglandin levels will be measured in blood in pg/mL	Baseline and directly after the administration of 6 hours atosiban
Side effect of atosiban	A potential side effect of atosiban is hyperglycaemia. Glucose levels will be measured in blood in mmol/l.	Baseline and directly after the administration of 6 hours atosiban

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (ACTUAL): May 19, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Tocolytic Agents; Atosiban
• Other Study ID Numbers: NL67501.091.18

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.: No