Translational Research in Pelvic Pain

NCT04001244 | Completed DMC

• 1 other identifier: TRiPP WP9
• Study Type: observational
• Target: 787
• Locations: 2 countries
• Sites: 2

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.

Conditions

Endometriosis; Bladder Pain Syndrome; Chronic Pain

Outcome Measures

Primary Outcomes (14)

• Quantitative Sensory Testing (QST)

  QST of the dorsal of the foot and midline lower abdomen according to the German Neuropathic Pain Network Protocol.

  1 year

• Presence of abdominal wall muscle tenderness

  Assessment of the abdominal wall specifically looking for muscle tenderness according to a standardised protocol (an enhanced Carnetts test as described by Scheltinga and Roumen 2017). Subjects will be categorised into muscle tenderness present or absent.

  1 year

• Change of pressure pain threshold (PPT)

  A standardised conditioned pain modulation (CPM) paradigm will be used to investigate the change in pressure pain threshold on the dorsum of the foot. An ischaemic stimulus to the contralateral arm will be used as the conditioned stimulus. The foot PPT will be measured before the conditioned stimulus and immediately after. The change will be reported as the (PPTbefore - PPTafter).

  1 year

• Area under the curve (AUC) of single day salivary cortisol profile

  Saliva will be collected at home at the specified times allowing a daily AUC of salivary cortisol for each subject to be calculated. Collection times: waking; 30-45 minutes after waking; before lunch; before dinner; bedtime.

  1 year

• Change in salivary cortisol

  A saliva sample will be collected at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as Cortisol(before)-Cortisol(after).

  Saliva collected immediately before and immediately after CPM paradigm (outcome 3).

• Heart rate (HR)

  Assessed over a 20 minute period at rest.

  1 year

• Change in heart rate

  Assessed at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as HR(before) - HR(after).

  HR assessed immediately before and immediately after the CPM paradigm (outcome 3)

• Blood pressure (BP)

  Assessed over a 20 minute period at rest. Measured in mmHG.

  1 year

• Change in Blood pressure

  Assessed at rest immediately before the CPM paradigm described in outcome 3 and then again immediately after. The ischaemic pain stimulus used as the conditioning stimulus in this paradigm is the most noxious component of the physiological testing paradigms used in this study and therefore the most likely to generate a stress response. The change will be reported as BP(before) - BP(after).

  BP assessed immediately before and immediately after the CPM paradigm (outcome 3)

• Bladder sensitivity to filling

  Assessed with standardised non-invasive bladder filling paradigm, measured as time to verbal reports of different sensations of bladder fullness (first sensation, first urge) and then need to void (maximum tolerance) after drinking 600 ml water. Subjects will be categorised into those with bladder sensitivity compared to published norms for reproductive age women and those with normal bladder sensation.

  1 year

• Volume voided at maximum tolerance

  Assessed with standardised non-invasive bladder filling paradigm described in outcome 10. The volume of urine voided when maximum tolerance is reached will be measured in mls.

  1 year

• fMRI scan

  fMRI scan with response to punctate stimuli of midline lower abdomen.

  1 year

• Pain Catastrophising: Pain Catastrophising Scale (PCS) (Sullivan)

  Measured with the Pain Catastrophising Scale (Sullivan). Scores range from 0 - 52 with high scores representing higher levels of pain catastrophising. Although three sub scales exist they will not be assessed for the purposes of these main analyses.

  Baseline

• Comorbid psychological distress

  Measured with the Hospital Anxiety and Depression Scale (HADS). Scores range from 0 - 21 for each of the two sub scales measuring anxiety and depression. The two sub scales will be summed as a unidimensional measure of psychological distress in initial analyses (0 - 42 with higher scores representing greater distress).

  Baseline

Secondary Outcomes (6)

• Metabolomic data

  Baseline

• Proteomic data

  Baseline

• Transcriptomic data

  Baseline

• Comorbidities

  Baseline

• Past trauma

  Baseline

Study Arms (5)

Endometriosis (EAP)

Surgical diagnosis of endometriosis (aim equal distribution of stage I/II and stage III/IV disease); at least one pelvic pain \>3/10; pain not perceived by the patient as arising from the bladder; no urinary symptoms (e.g. urge, frequency)

Bladder Pain Syndrome (BPS)

Bladder pain syndrome (as defined by 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); no history of endometriosis

Endometriosis and Bladder Pain (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)

Controls

No endometriosis; No pelvic pain (or dysmenorrhea; NRS \<3/10)

Pelvic Pain (PP)

At least one pelvic pain \>3/10; no endometriosis; pain not perceived by the patient as arising from the bladder; no urinary symptoms (e.g. urge, frequency)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• 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:
• Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
• And for fMRI:
• fMRI compatible.
• Contraindication to fMRI scan i.e. metallic implants, stents, clips, weight greater than acceptable for local fMRI scanner etc.

Sponsors & Collaborators

• University of Oxford: lead
• Boston Children's Hospital: collaborator
• Michigan State University: collaborator
• Bayer: collaborator
• Grünenthal GmbH: collaborator
• Esteve: collaborator
• Queen Mary University of London: collaborator
• Aalborg University: collaborator
• Endometriosis.org: collaborator
• International Painful Bladder Foundation: collaborator
• Pelvic Pain Support Network: collaborator
• King's College London: collaborator
• Heidelberg University: collaborator
• University of Edinburgh: collaborator
• University of Jena: collaborator
• Universität Münster: collaborator
• Universidade do Porto: collaborator

Study Sites (2)

IBMC

Porto, Portugal

Location

University of Oxford

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Related Links

• Project website as part of the overall project IMI-PainCare that TRiPP sits within

Biospecimen

Retention: SAMPLES WITH DNA

Saliva Blood Urine Bladder biopsies (for BPS patients) Eutopic and ectopic endometrium (for endometriosis patients and Oxford controls) N.B. Biospecimens have already been collected for all Endometriosis (with and without bladder symptoms) and Control subjects, therefore new bio specimens are only being collected for the BPS cohort or if necessary for additional analyses (e.g. salivary cortisol), in which case samples will not be retained.

MeSH Terms

Conditions

Endometriosis; Cystitis, Interstitial; Chronic Pain

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Cystitis; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Katy Vincent, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: June 28, 2019
• Study Start: September 1, 2019
• Primary Completion: September 1, 2021
• Study Completion: February 23, 2023
• Last Updated: April 4, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available once all analyses are complete.
• Access Criteria: Data will be publically accessible

Locations

PT (1); GB (1)