Clinical trial NCT04001244: Translational Research in Pelvic Pain
Official title: Translational Research in Pelvic Pain. Deep Phenotyping of Women With Endometriosis-associated Pain and Bladder Pain Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Endometriosis
Bladder Pain Syndrome
Chronic Pain
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Michigan State University
name: Bayer
name: Grünenthal GmbH
name: Esteve
name: Queen Mary University of London
name: Aalborg University
name: Endometriosis.org
name: International Painful Bladder Foundation
name: Pelvic Pain Support Network
name: King's College London
name: Heidelberg University
name: University of Edinburgh
name: University of Jena
name: Universität Münster
name: Universidade do Porto
First posted: 2019-06-28
Enrollment: 787
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Controls, EAP and EABP will be selected from already recruited cohorts, with permission to be recontacted, in the ENDOX (University of Oxford) and BCE (Boston Childrens Hospital) studies. BPS will be recruited from secondary/tertiary care clinics and from adverts on patient support group sites and in local media.

Brief summary: This study aims to better understand the pathways leading to pain in women with two types of pelvic pain condition (endometriosis-associated pain and bladder pain syndrome) and determine whether these pathways can be used to subgroup patients.

Detailed description: Chronic pelvic pain is as common as asthma, migraine and back pain and has a very significant impact on quality of life. However, it is still poorly understood and the available treatments are limited and often not successful. This project focuses on two causes of chronic pelvic pain: endometriosis and interstitial cystitis/bladder pain syndrome. Endometriosis (the presence of tissue resembling the lining of the womb outside of the womb) is very common, affecting \~1 in 10 women, and is associated with often disabling pelvic pain symptoms including painful periods, pain throughout the month, and pain associated with sex, passing urine and opening bowels. Interstitial cystitis/bladder pain syndrome is much less common but dramatically reduces quality of life with many women planning their day around trips to the toilet.

This multi-centre study will be carried out at 3 sites in Europe and 1 in the U.S.. Rather than focusing on the pelvis, the investigators will approach these conditions in the context of other chronic pain conditions with which they share many features and thus consider the many different systems that might contribute to generating and maintaining pain. The investigators will combine detailed clinical and questionnaire data with tests of the function of a variety of systems (including nerve function, stress response and psychology) and the results of analyses of different body fluids and tissues (including blood, urine, endometriosis lesions). No study treatment or intervention will be given during TRiPP. The aim is to identify pathways responsible for pain in these women and determine whether they can be divided into subgroups on the basis of different pain pathways that might therefore respond to different treatments. Ultimately the investigators hope to identify new targets for treatment and contribute to the design of more personalised treatment plans.

Eligibility criteria: Inclusion Criteria:

* Female, aged 18 - 50 years.
* Participant is willing and able to give informed consent for participation in the study.
* EAP/EABP/CON: previously enrolled in EndOX or BCE cohorts with consent to be contacted again.
* EAP: Surgical diagnosis of endometriosis; at least one pelvic pain \>3/10.
* EABP: Surgical diagnosis of endometriosis; at least one pelvic pain \>3/10; pain perceived by the patient as arising from the bladder AND from other area(s) of the pelvis; at least one urinary symptom (e.g. urge, frequency).
* BPS: fulfil ESSIC criteria (Pelvic pain, pressure or discomfort for greater than 6 months, perceived to be related to the urinary bladder accompanied by at least one other urinary symptom like persistent urge to void or frequency).

Exclusion Criteria:

* Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
* EAP: pain perceived by the patient as arising from the bladder; urinary symptoms (e.g. urge, frequency).
* CON: previous diagnosis of endometriosis; pelvic pain or dysmenorrhoea (NRS\>3/10)
* BPS: previous diagnosis of endometriosis.

Additionally, for physiological testing:

Exclusion:

• Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

And for fMRI:

Inclusion:

• fMRI compatible.

Exclusion:

* Contraindication to fMRI scan i.e. metallic implants, stents, clips, weight greater than acceptable for local fMRI scanner etc.
* Use of centrally acting drugs in the previous 3 months (e.g. anti-epileptics, anti-depressants, anxiolytics, gabapentin, pregabalin, duloxetine). N.B. Regular use of standard analgesics including opiates is not an exclusion criterion, however, women will be asked to refrain from taking such drugs for 8 hours prior to their brain scan if at all possible.

Primary outcomes:
measure: Quantitative Sensory Testing (QST)
timeFrame: 1 year
measure: Presence of abdominal wall muscle tenderness
timeFrame: 1 year
measure: Change of pressure pain threshold (PPT)
timeFrame: 1 year
measure: Area under the curve (AUC) of single day salivary cortisol profile
timeFrame: 1 year
measure: Change in salivary cortisol
timeFrame: Saliva collected immediately before and immediately after CPM paradigm (outcome 3).
measure: Heart rate (HR)
timeFrame: 1 year
measure: Change in heart rate
timeFrame: HR assessed immediately before and immediately after the CPM paradigm (outcome 3)
measure: Blood pressure (BP)
timeFrame: 1 year
measure: Change in Blood pressure
timeFrame: BP assessed immediately before and immediately after the CPM paradigm (outcome 3)
measure: Bladder sensitivity to filling
timeFrame: 1 year
measure: Volume voided at maximum tolerance
timeFrame: 1 year
measure: fMRI scan
timeFrame: 1 year
measure: Pain Catastrophising: Pain Catastrophising Scale (PCS) (Sullivan)
timeFrame: Baseline
measure: Comorbid psychological distress
timeFrame: Baseline
Secondary outcomes:
measure: Metabolomic data
timeFrame: Baseline
measure: Proteomic data
timeFrame: Baseline
measure: Transcriptomic data
timeFrame: Baseline
measure: Comorbidities
timeFrame: Baseline
measure: Past trauma
timeFrame: Baseline
measure: Recent trauma
timeFrame: Baseline
Other outcomes:
Locations:
city: Porto
country: Portugal
facility: IBMC
city: Oxford
country: United Kingdom
facility: University of Oxford
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Katy Vincent, DPhil
role: PRINCIPAL_INVESTIGATOR
References: