Pain Type and Interstitial Cystitis/Bladder Pain Syndrome Treatment

Official title

Mechanistic-Based Treatment of Interstitial Cystitis/Bladder Pain Syndrome

Overview

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a severe pain condition affecting 3-8 million people in the United States lacking treatments that work. Emotional suffering is common in IC/BPS and known to make physical symptoms worse, and studies show patient sub-groups respond differently to treatment. Individuals with IC/BPS have distinct subgroups, or "phenotypes," largely characterized by the distribution of pain throughout the body. Supported by our preliminary evidence, the overall goal of this project is to assess how IC/BPS phenotype may affect response to two different therapies often given without regard to patient phenotype, pelvic floor physical therapy (PT) and cognitive-behavioral therapy (CBT) for IC/BPS.

Detailed description

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating, incurable, and costly pain condition affecting approximately 3-8 million individuals in the United States and is extremely challenging to treat. Treatment advances in IC/BPS have stalled due to a lack of clear understanding of the condition, as symptoms and presentations vary widely. For these reasons, national organizations have prioritized the need to improve both treatment options and understanding of IC/BPS. Leading multi-institutional research networks have now identified that individuals with IC/BPS have distinct subgroups, or "phenotypes," largely characterized by the distribution of pain throughout the body. At the same time, the chronic pain field is adopting a new approach driven by mechanisms of illness and treatment. Growing evidence suggests that different phenotypes of patients with IC/BPS respond differently to medical intervention. The overall goal of this project is to assess how IC/BPS phenotype may affect response to two different therapies often given without regard to patient phenotype, pelvic floor physical therapy (PT) and cognitive-behavioral therapy (CBT) for IC/BPS. The investigator is proposing a randomized mechanistic trial to evaluate which participants may benefit from each treatment (Aim 1) and evaluate whether neurobiological mechanisms may moderate outcomes and change with treatment (Aim 2). The investigator hypothesizes that a prediction of which participants will respond preferentially to either form of treatment based on reported bodily pain distribution (pelvic pain primarily, pain outside of the pelvis). This project has great potential to tailor treatment and improve future IC/BPS precision-medicine care efforts.

Interventions

• Behavioral Psychosocial Treatment
  The psychosocial self-management intervention consists of 8 weekly 50-minute individual visits with an assigned trained therapist. Sessions follow a structured protocol that has been developed with the patient population and tested in a prior study. Treatment modules are individualized and include topics such as pain coping strategies, relaxation training, education on IC/BPS, and communication strategies.
• Other Pelvic Floor Physical Therapy
  The pelvic floor physical therapy condition consists of 10 weekly 45-minute individual visits with an assigned trained physical therapist. In IC/BPS, pelvic floor physical therapy (PT) uses manual manipulation to release localized muscle tension, trigger points, and correct other scars and restrictions to reduce pain and urgency symptoms. Specific techniques will include external connective tissue manipulation to the abdominal wall, back, buttocks and thighs, myofascial trigger point release, an

Primary outcome measures

• Differences in response to treatment by phenotype measured by the Global Response Assessment (GRA) scale. [Time frame: Post-treatment (either Week 8 or 10)]

Secondary outcome measures (7)

• Chronic Overlapping Pain Condition-Screener (COPCS) [Time frame: Baseline (Week 0)]
• Quantitative Sensory Testing - Tolerance Average (QST-TOL) [Time frame: Baseline (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]
• Quantitative Sensory Testing - Threshold Average (QST-THR) [Time frame: Baseline (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]
• Quantitative Sensory Testing - Temporal Summation (QST-TS) [Time frame: Baseline, (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]
• Urinary Nerve Growth Factor (NGF) [Time frame: Baseline, (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]
• Urinary Interleukin-6 (IL6) [Time frame: Baseline, (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]
• Interleukin-6, whole blood stimulated (IL6-LPS) [Time frame: Baseline, (Week 0), Post-treatment (either Week 8 or 10), Follow-up (Week 24)]

Eligibility criteria

Inclusion criteria

• 18 years of age or older;
• Diagnosis of IC/BPS as indicated by structured assessments;
• Capable of giving written informed consent;
• Able to enroll for the duration of the study period;

Exclusion criteria

• Comorbid neurological conditions including spinal cord injury or systematic neurologic illnesses, or central nervous system diseases such as brain tumor or stroke;
• Current or history of diagnosis of primary psychotic or major thought disorder within the past five years;
• Hospitalization for psychiatric reasons other than suicidal ideation, homicidal ideation, and/or PTSD (within the past 5 years);
• Psychiatric or behavioral conditions in which symptoms are unstable or severe (e.g. current delirium, mania, psychosis, active suicidal ideation, homicidal ideation, substance abuse dependency) reported within the past six months;
• Non-English speaking;
• Presenting symptoms at time of screening that would interfere with participation, specifically active suicidal ideation with intent to harm oneself or active delusional or psychotic thinking;
• Difficulties or limitations communicating over the telephone or via teleconferencing systems;
• Any planned life events that would interfere with participating in the key elements of the study;
• Any major active medical issues that could preclude participation;
• Currently pregnant;
• Currently being treated for cancer;
• Cancer-related pain;
• Recently or actively participating in treatment similar to those being investigated (e.g. individual psychotherapy or pelvic floor pt).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Vanderbilt Urology Cool Springs — Franklin

Publications

• Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM; Interstitial Cystitis Guidelines Panel of the American Urological Association Education and Research, Inc. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011 Jun;185(6):21 PMID 21497847
• Rampakakis E, Ste-Marie PA, Sampalis JS, Karellis A, Shir Y, Fitzcharles MA. Real-life assessment of the validity of patient global impression of change in fibromyalgia. RMD Open. 2015 Sep 14;1(1):e000146. doi: 10.1136/rmdopen-2015-000146. eCollection 2015. PMID 26535150
• Sherman AL, Morris MC, Bruehl S, Westbrook TD, Walker LS. Heightened Temporal Summation of Pain in Patients with Functional Gastrointestinal Disorders and History of Trauma. Ann Behav Med. 2015 Dec;49(6):785-92. doi: 10.1007/s12160-015-9712-5. PMID 25967582
• Starkweather AR, Heineman A, Storey S, Rubia G, Lyon DE, Greenspan J, Dorsey SG. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain. Appl Nurs Res. 2016 Feb;29:237-41. doi: 10.1016/j.apnr.2015.03.013. Epub 2015 Apr 8. PMID 26856520
• Li J, Simone DA, Larson AA. Windup leads to characteristics of central sensitization. Pain. 1999 Jan;79(1):75-82. doi: 10.1016/S0304-3959(98)00154-7. PMID 9928779
• Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giuliani MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH; Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003 Mar 25;60(6):898-904. doi: 10.1212/01.wnl.0000058546 PMID 12654951
• Ezenwa MO, Molokie RE, Wang ZJ, Yao Y, Suarez ML, Pullum C, Schlaeger JM, Fillingim RB, Wilkie DJ. Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain? Pain Pract. 2016 Mar;16(3):282-93. doi: 10.1111/papr.12279. Epub 2015 Jan 12. PMID 25581383
• Schrepf A, Maixner W, Fillingim R, Veasley C, Ohrbach R, Smith S, Williams DA. The Chronic Overlapping Pain Condition Screener. J Pain. 2024 Jan;25(1):265-272. doi: 10.1016/j.jpain.2023.08.009. Epub 2023 Aug 24. PMID 37633574

Identifiers

NCT: NCT06299683 · 230487 · 1R01DK133415-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗