Clinical trial NCT05127616: EPPIC: Easing Pelvic Pain Interventions Clinical Research Program
Official title: A Brief, Transdiagnostic Cognitive Behavioral Treatment for Urological Chronic Pelvic Pain Syndrome: Processes, Predictions, Outcomes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Urologic Chronic Pelvic Pain Syndrome (UCPPS)
Interstitial Cystitis
Bladder Pain Syndrome
Chronic Prostatitis
Chronic Pain
Chronic Pelvic Pain Syndrome
Chronic Overlapping Pain Disorders
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: University of Michigan
First posted: 2021-11-19
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The EPPIC (Easing Pelvic Pain Interventions Clinical Research Program) study evaluates an ultra-brief, 4 session cognitive behavioral pain treatment transdiagnostic in design for urologic chronic pain syndrome (UCPPS) with clinical and practical advantages over existing behavioral therapies whose length and focus limits their adoption by clinicians and coverage for mechanistically similar comorbidities. A theoretically informed, practical, empirically grounded approach will systematically unpack CBT's working mechanisms, clarify for whom it works, ease dissemination, appeal to patients, providers, payers, and policy makers in the COVID-19 era favoring low resource intensity treatments, and reduce cost and inefficiencies associated with high intensity therapies whose complexity, length, and scarcity restricts uptake and impact.

Detailed description: Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated. Their prolonged personal and economic costs are amplified by the frequent co-occurrence of a cluster of centralized pain conditions (particularly irritable bowel syndrome 3 \[IBS\]) but also fibromyalgia \[FMS\], chronic headache, chronic fatigue, etc.) called Chronic Overlapping Pain Conditions (COPC). Clinically, the notion that these syndromes share a centralized pain phenotype with a fundamental disturbance in pain or sensory processing dovetails with our preliminary research showing that a novel transdiagnostic behavioral treatment emphasizing a single common mechanistic pathway (i.e. inflexible cognitive style) reduces severity of both targeted (IBS) and untargeted multisymptom COPCs that include (but is not limited to) to UCPPS, FMS, chronic fatigue, and chronic headache. If effective in a larger scale study, a transdiagnostic UCPPS treatment would offer a more efficient, accessible, and broadly useful strategy for improving chronic pelvic pain and its most frequent and complicating comorbidities. To this end, the investigators will randomize 240 UCPPS subjects (18-70 yrs.) of any gender and race to a 4-session version of CBT that teaches skills for self-managing UCPPS symptoms (e.g. pelvic pain, urinary symptoms such as urinary frequency, urgency) with minimal clinician oversight (MC-CBT) or a four-session non-specific education/support control (EDU). Efficacy assessments will be administered at pre-treatment baseline and two weeks after the end of the 10-week acute phase using the patient version of the Clinical Global Impressions Scale and validated with the physician version rated by MD assessors blind to treatment assignment. The investigators hypothesize MC-CBT will deliver significantly greater UCPPS symptom improvement than EDU (Aim 1). Additional aims include characterizing the durability of effects 3- and 6 months post treatment (Aim 2). To increase the efficacy and efficiency of behavioral pain treatments, the investigators draw upon Beck's transdiagnostic cognitive model to characterize the precise cognitive procedures and corresponding operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT induced UCPPS symptom relief relative to EDU (Aim 3) as well as baseline patient variables that moderate differential response (Aim 3) with the ultimate goal of more proactive patient-treatment matching fundamental to the goals of personalized medicine. By applying innovative statistical modelling (e.g. dominance analysis, Randomized Explanatory Trial analyses) to study aims in the context of a rigorously designed behavioral trial, the researchers expand the portfolio of nondrug pain treatments for UCPPS and co-aggregating COPCs to include one whose brevity, convenience, and transdiagnostic design "meets patients where they are" and addresses the practical (access, complexity, cost), clinical (breadth, durability, magnitude of effects, patient preference) and conceptual (untargeted comorbidities, non-pain somatic symptoms) challenges that have impeded uptake and public health impact of evidence-based behavioral pain treatments at a time when our most vulnerable high impact pain patients are in greatest need.

Eligibility criteria: Inclusion Criteria:

* Ages 18-70 years (inclusive)
* Male or female
* All genders, races, ethnic groups
* MD-confirmed diagnosis of IC/BPS or CP/CPPS by study urologist or urogynecologist
* Pelvic pain including uncomfortable sensations of pressure or discomfort that are not described as outright pain) of at least six months duration
* Pelvic pain intensity of at least moderate severity (defined as 3 or greater on a 0-10 Numerical Rating Scale and causes life interference weekly and limit(s) participant's life or work-related activities, general activity level, and/or enjoyment of life) over the past 3 months.
* Ability to understand and provide informed consent
* Either not taking medications or if taking medications willing to refrain from starting new medications until after the initial 2-week pre-treatment baseline period ends unless medically necessary.
* A minimum 6th grade reading level based on the Wide Range Achievement Test (WRAT 4)
* Willing to be randomized to either CBT or Support/Education and to follow the protocol to which s/he has been assigned
* Willing to be contacted for follow up assessments at week 12 and 3, 6 months after treatment ends
* Willing to attend sessions
* Able to maintain symptom diaries and complete paper work
* Access to telephone and computer or smartphone
* Willing and able to provide adequate information for locator purposes

Exclusion Criteria: Urologic-Specific

* Presence of a neurological condition (e.g., MS, Parkinson's disease, paraplegia) affecting the bladder
* The presence of a symptomatic urethral stricture (males only)
* History of cystitis caused by tuberculosis or radiation or chemotherapies
* Participant has been diagnosed and treated for a pelvic-related malignancy (colon, bladder, prostate, ovarian, endometrial, uterine, testicular, penile, cervical, vaginal, or rectal cancer)

Exclusion Criteria: General

* Participant has a medical condition(s) whose nature or severity (unstable, life threatening, etc.) would influence adversely the conduct of the clinical trial, confound interpretation of study results, and/or compromise volunteer safety and engagement with study demands.
* Gross cognitive impairment, deafness, blindness, vision problems (severe), hearing problems (severe)
* Has a major psychiatric disorder which would impede conduct of the clinical study. These clinical disorders would include but are not limited to major depression with a high risk of suicidal behavior (i.e. intent or plan), current or recent (within the past 3 months) history of alcohol or substance abuse/dependence, a lifetime history of schizophrenia or schizoaffective disorder; or organic mental disorder
* Current involvement in psychotherapy directed specifically toward relief of urological symptoms
* Schedule does not permit participation in clinic sessions or home practice including plans to move out of the area, lack of reliable transportation, etc.
* Characteristics related to inability to complete the study protocol
* Unable to read or fluently speak English
* Inability to complete screening visits
* Inaccessible for interventions and/or follow up evaluations

Primary outcomes:
measure: Clinical Global Impressions - Improvement Scale Patient Version (CGI-I)
timeFrame: 12 weeks after pre-treatment baseline
Secondary outcomes:
measure: Genitourinary Pain Index (GUPI)
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Interstitial Cystitis Problem Index (ICPI)
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Interstitial Cystitis Symptom Index (ICSI)
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Brief Symptom Inventory (BSI 18)
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: PROMIS - Pain Interference SF-6a
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Client Satisfaction Questionnaire (CSQ)
timeFrame: 12 weeks after pre treatment baseline
Other outcomes:
measure: PROMIS - Fatigue SF-7a
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: PROMIS Scale v1.2-Global Health Physical 2a
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: PROMIS Scale v1.2-Global Health Mental 2a
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Beck Depression Inventory - II (BDI-II)
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: SF-12 Health Survey
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
measure: Change from baseline of the PROMIS - Sleep Disturbance SF-8b
timeFrame: Baseline, 12 weeks after pre treatment baseline, 3- and 6-month follow-up
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: University at Buffalo (the only clinical site where treatment is delivered)
state: New York
Study officials:
affiliation: University at Buffalo (SUNY)
name: Jeffrey Lackner, PsyD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clemens JQ, Mullins C, Ackerman AL, Bavendam T, van Bokhoven A, Ellingson BM, Harte SE, Kutch JJ, Lai HH, Martucci KT, Moldwin R, Naliboff BD, Pontari MA, Sutcliffe S, Landis JR; MAPP Research Network Study Group. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol. 2019 Mar;16(3):187-200. doi: 10.1038/s41585-018-0135-5.
citation: Leue C, Kruimel J, Vrijens D, Masclee A, van Os J, van Koeveringe G. Functional urological disorders: a sensitized defence response in the bladder-gut-brain axis. Nat Rev Urol. 2017 Mar;14(3):153-163. doi: 10.1038/nrurol.2016.227. Epub 2016 Dec 6.
citation: Lackner JM, Jaccard J, Quigley BM, Ablove TS, Danforth TL, Firth RS, Gudleski GD, Krasner SS, Radziwon CD, Vargovich AM, Clemens JQ, Naliboff BD. Study protocol and methods for Easing Pelvic Pain Interventions Clinical Research Program (EPPIC): a randomized clinical trial of brief, low-intensity, transdiagnostic cognitive behavioral therapy vs education/support for urologic chronic pelvic pain syndrome (UCPPS). Trials. 2022 Aug 13;23(1):651. doi: 10.1186/s13063-022-06554-9.