Platelet Activating Factor Stability in Urine

The investigator's hypothesis is that smoking induces inflammation in the bladder wall. This may predispose to the development of Interstitial cystitis(IC) / bladder pain syndrome(BPS). Previous research has linked one the Platelet Activating Factor - PAF to interstitial cystitis. The investigators will study a limited number of patients to determine whether PAF is stable in urine and whether special precautions (for example - immediate freezing in liquid nitrogen) is necessary for accurate measurement of PAF in the urine.

Patients who are presenting for an office visit will be asked to donate at least 50 ml of urine.

A separate group of patients who are scheduled for surgery, are also being asked to donate around 25 ml of urine during surgery.

No patient data other than group assignment, whether they smoke or if they have or not have interstitial cystitis will be recorded.

Study Overview

• Status: Completed
• Conditions: Interstitial Cystitis
• Intervention / Treatment: Other: Urine stability

Detailed Description

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a severe, chronic bladder condition that is extremely painful and disruptive. Incidence of the disease has increased dramatically in recent years, primarily due to enhanced awareness and better defined inclusion criteria. Difficulty in diagnosis arises from the diversity of symptoms and severity between patients and in the same patient at different times. IC/BPS is generally accepted as a disease of exclusion in which a diagnosis is reached after ruling out other conditions. A firm diagnosis is only mildly assuring for patients because there are very few therapeutic approaches that can alleviate the symptoms. Several risk factors are associated with IC/BPS, including age, sex and race [5] and modifiable risk factors such as diet and smoking. This proposal is to test the hypothesis that cigarette smoking contributes directly to changes in the bladder that are indicative of, or predispose to, IC/BPS. In preliminary studies, the investigators have exposed mice to cigarette smoke and observed breaks in the urothelium, decreased urothelial tight junction protein expression, increased vascularity and inflammatory cells in the bladder wall. This lab has previously demonstrated that cigarette smoke inhibits endothelial cell platelet activating factor acetylhydrolase (PAF-AH), which is responsible for the hydrolysis of PAF, resulting in increased PAF, a membrane phospholipid-derived inflammatory mediator. The investigators have also shown that calcium-independent phospholipase A2β (iPLA2β) is responsible for the majority of PAF production in endothelial and urothelial cells. PAF has been shown to increase matrix metalloproteinases (MMP) which in turn inhibit anti-angiogenic pigment epithelium-derived factor (PEDF), thus promoting angiogenesis. These studies indicate a direct relationship between PAF accumulation and PEDF expression in the bladder that may contribute to inflammation in smokers.

PAF stability in urine has not been established in the literature. This study is proposing to assess PAF and PAF-AH activity in urine after using various handling methods of the urine specimen. Better understanding of PAF stability will allow for better design of future experiments involving PAF in interstitial cystitis patients.

The investigators have exposed mice to cigarette smoke and examined changes in the bladder. they have observed thinning and sloughing of the urothelium, plus increased vascularization. These changes are observed in the bladder wall of IC/BPS patients. We have measured increased PAF accumulation and decreased expression of PEDF in the bladder wall.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • St. Mary's Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Adult females with r without IC

Description

Inclusion Criteria:

• Patient presenting for routine care in the UroGynecology division or
• Patient undergoing gynecologic or urogynecologic surgery exceeding 60 minute operating time.

Exclusion Criteria:

• Age less than 18 or more than 80
• Unable to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Office; Patients presenting for a routine office visit will be asked to donate at least 50 ml of urine. The urine specimen will be aliquoted in containers, one with and one without a PAF-AH inhibitor and kept at room temperature. The aliquots (2mL) will be frozen at predetermined intervals of 5, 10, 20, 40 and 60 min from time of collection in liquid nitrogen and then later stored in -80 freezer.	Other: Urine stability; This study is proposing to assess PAF and PAF-AH activity in urine after using various handling methods of the urine specimen. Better understanding of PAF stability will allow for better design of future experiments involving PAF in interstitial cystitis patients.
Surgery; A separate group of patients undergoing surgery lasting more than 60 min operating time, will be consented as well. These patients have Foley catheters in place during the surgery. Five cc's of urine will be collected from the catheter at pre-determined intervals 5, 10, 20, 40 and 60 minutes, aliquoted (2mL) and frozen in liquid nitrogen and later stored in the -80 freezer.	Other: Urine stability; This study is proposing to assess PAF and PAF-AH activity in urine after using various handling methods of the urine specimen. Better understanding of PAF stability will allow for better design of future experiments involving PAF in interstitial cystitis patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PAF production	elicits changes in the bladder wall that can predispose to IC/BPS. In this aim, the investigators will determine whether urine PAF is stable at room temperature, or whether special precautions (e.g. freezing or use of PAF-AH inhibitors) are needed for accurate PAF measurements in urine samples.	1 hour

Collaborators and Investigators

• Sponsor: St. Louis University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2017
• Primary Completion (ACTUAL): February 28, 2017
• Study Completion (ACTUAL): February 28, 2017

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (ACTUAL): April 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Cystitis; Cystitis, Interstitial
• Other Study ID Numbers: 27756

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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