Effects of Epigenetic Regulation in Chronic Pelvic Pain Syndrome

This study seeks to identify defects in immune activation or regulation that may affect a subset of patients with CP/CPPS. This subset appears to have a reduced ability to mount a regulatory immune response, while simultaneously eliciting an exaggerated activated immune response. The defects that we demonstrate appear to be linked to altered methylation of genes involved in both immune regulation and immune activation. The aims of this study will provide definitive evidence of a role for epigenetic changes in immune cells in patients with CP/CPPS.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pelvic Pain

Detailed Description

CPPS is a condition that is estimated to affect up to 15% of the male population with most diagnoses between the ages of 35-45. Designated by the presence of pain in the absence of bacterial infection for more than three months, it has unknown, probably complex etiology, which thus far have hampered efforts to determine effective treatment strategies. The heterogeneous nature of the symptoms and the length of the disease course prior to detection, presentation or diagnosis only further exacerbate these issues. This study seeks to identify defects in immune activation or regulation that may affect a subset of patients with CP/CPPS. This subset appears to have a reduced ability to mount a regulatory immune response, while simultaneously eliciting an exaggerated activated immune response. The defects that we demonstrate appear to be linked to altered methylation of genes involved in both immune regulation and immune activation. The aims of this study will provide definitive evidence of a role for epigenetic changes in immune cells in patients with CP/CPPS. This is conceptually a major advance - as a variety of factors including early life stress events, prostate infectious agents, environmental variables, all could contribute to epigenetic change and may therefore explain both the anecdotal etiologies described in this syndrome as well as the difficulty in pinpointing a precise etiological mechanism. Specifically, our data leads us to hypothesize that epigenetic alterations in regulatory and proinflammatory immune pathways underpin the development of chronic pelvic pain in CPPS. In this study, we propose to validate our preliminary findings in a larger set of CP/CPPS patients and controls as well as utilize murine models of prostatitis to understand the mechanism driving altered IL-10 and IL-7/LFA-1 mediated immune responses both at systemic and prostate levels. If epigenetic defects and functional deficits can be demonstrated, diagnosis and treatment methodologies could be better targeted at correction of these chronic deficits rather than at etiological agents/pathways that are in the past.

BACKGROUND:

Prostatitis accounts for approximately 2 million outpatient visits per year in the United States, including 1% of those to primary care physicians. Chronic pelvic pain syndrome (CPPS) accounts for 90% of all chronic prostatitis but has no well-defined etiology. It is clinically characterized by the symptoms of pain in the perineum, testes, penis, suprapubic area, dysuria and profound reductions in patient quality of life. Epidemiologic observations indicate that prostatitis conditions are the most frequent urologic diagnosis in young men and the third most frequent urologic diagnosis in men older than 50 yr, representing 8-12% of urology office visits. The NIH consensus definition and classification identifies four categories of prostatitis. Categories I and II have bacterial etiologies while the rest are believed to be non- bacterial in etiology.

Category III is subdivided into inflammatory (IIIa) and noninflammatory (IIIb) subtypes, based on the presence of white blood cells in expressed prostatic secretions (EPS). Category III prostatitis or chronic pelvic pain syndrome (CPPS) is the most common prostatitis observed in medical practice with a prevalence rate in the general population from 5% to 14.2%. CPPS is a poorly understood entity characterized by pelvic or perineal pain, irritative voiding symptoms, and sexual dysfunction.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

We hypothesize that aberrant immune regulation and/or activation due to epigenetic alterations in immune genes facilitate chronic pelvic pain. The objective of this aim is to expand on our preliminary data demonstrating epigenetic modifications in immune-related genes in CP/CPPS patients compared to healthy controls. To do so, we propose to recruit CP/CPPS patients and healthy volunteers to obtain peripheral blood and prostate secretions (EPS) for performing tailored methylation arrays on PBMC's, examination of functional consequences of immune alterations and finally correlation with patient symptoms.

Description

Inclusion Criteria:

Inclusion Criteria for Control Group:

• Healthy males ages 21-80 years old

Exclusion Criteria:

Exclusion Criteria for Control Group:

• Females
• Males <21 and >80 years old
• Patients with impaired renal or hepatic function.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Males with Category III Chronic Pelvic Pain Syndrome; Category III is subdivided into inflammatory (IIIa) and noninflammatory (IIIb) subtypes, based on the presence of white blood cells in expressed prostatic secretions (EPS). Category III prostatitis or chronic pelvic pain syndrome (CPPS) is the most common prostatitis observed in medical practice with a prevalence rate in the general population from 5% to 14.2%. CPPS is a poorly understood entity characterized by pelvic or perineal pain, irritative voiding symptoms, and sexual dysfunction.
Control Group; The control group will consist of men with no history of Chronic Pelvic Pain or any underlying condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identifying immune-related epigenetic modifications in patients with CP/CPPS.	To recruit CP/CPPS patients and healthy volunteers to obtain peripheral blood and prostate secretions (EPS) for performing epigenetic analysis of PBMC	5 Years
Identifying immune-related modifications in patients with CP/CPPS.	To recruit CP/CPPS patients and healthy volunteers to obtain peripheral blood and prostate secretions (EPS) for examination of immune changes.	5 Years
Identifying patient symptoms in CP/CPPS.	To recruit CP/CPPS patients and healthy volunteers to obtain peripheral blood and prostate secretions (EPS) for examining correlation with patient symptoms.	5 Years

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Praveen Thumbikat, PhD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 11, 2025

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pelvic Pain
• Other Study ID Numbers: STU00215831

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No