Translational Research in Pelvic Pain

Chronic Pain Clinical Trial

— TRiPP  

Official title:

Translational Research in Pelvic Pain. Deep Phenotyping of Women With Endometriosis-associated Pain and Bladder Pain Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04001244
• Other study ID #: TRiPP WP9
• Status: Completed
• Start date: September 1, 2019
• Est. completion date: February 23, 2023

Study information

• Verified date: November 2022
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 787
• Est. completion date: February 23, 2023
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Pain Syndrome
• Chronic Pain
• Cystitis, Interstitial
• Endometriosis
• Pelvic Pain
• Syndrome

Locations

Country	Name	City	State
Portugal	IBMC	Porto
United Kingdom	University of Oxford	Oxford	Oxfordshire

Sponsors (17)

Lead Sponsor	Collaborator
University of Oxford	Aalborg University, Bayer, Boston Children's Hospital, Endometriosis.org, Esteve, Grünenthal GmbH, Heidelberg University, International Painful Bladder Foundation, King's College London, Michigan State University, Pelvic Pain Support Network, Queen Mary University of London, Universidade do Porto, University of Edinburgh, University of Jena, Westfälische Wilhelms-Universität Münster

Countries where clinical trial is conducted

Portugal,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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).
Primary	Heart rate (HR)	Assessed over a 20 minute period at rest.	1 year
Primary	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)
Primary	Blood pressure (BP)	Assessed over a 20 minute period at rest. Measured in mmHG.	1 year
Primary	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)
Primary	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
Primary	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
Primary	fMRI scan	fMRI scan with response to punctate stimuli of midline lower abdomen.	1 year
Primary	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
Primary	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	Metabolomic data	Discovery study of levels of all known metabolite in plasma using an established validated proprietary tool designed by Metabolon (https://www.metabolon.com).	Baseline
Secondary	Proteomic data	Study measuring levels of proteins detected on two panels (inflammation and neurological) as designed by OLink (https://www.olink.com).	Baseline
Secondary	Transcriptomic data	Discovery transcriptomic analysis of matched eutopic and ectopic endometrium from endometriosis and control women will be performed on a subgroup of participants. Both descriptive data and pathway analysis will be performed.	Baseline
Secondary	Comorbidities	Assessed with the complex medical symptoms inventory (CMSI).; The CMSI contains a 41 item symptom screener, which an increasing score on adds up to a higher functional somatic burden (scores range from 0-41). Additionally, clusters of symptoms point to specific diagnoses for which the full diagnostic criteria questions are provided allowing the commonest overlapping pain conditions to be screened for: Fibromyalgia temporomandibular disorders irritable bowel syndrome chronic tension type headache migraine chronic low back pain myalgic encephalitis/chronic fatigue syndrome interstitial cystitis/painful bladder syndrome endometriosis vulvodynia	Baseline
Secondary	Past trauma	Assessed with the Childhood Traumatic Events Scale (CTES). Scores range from 0 - 42 with higher scores representing more experience of early trauma. No sub scales will be derived.	Baseline
Secondary	Recent trauma	Assessed with the Recent Traumatic Events Scale (RTES). Scores range from 0 - 42 with higher scores representing more experience of recent trauma. No sub scales will be derived.	Baseline

External Links

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