Intestinal Permeability and Endometriosis

Completed

• Conditions: Endometriosis

• Registration Number: NCT03042923
• Lead Sponsor: University of Tennessee

Brief Summary

The objective of this project will be to determine whether patients with a surgical diagnosis of endometriosis have impaired intestinal permeability as compared with healthy controls. This would suggest the presence of an environmentally triggered and intestinally mediated association in the etiology of endometriosis. This would be a proof of concept trial to establish whether there is in fact a relationship worthy of future research.

Detailed Description

Twenty patients with a clinical diagnosis of endometriosis who are scheduled for surgical evaluation will be eligible for the study arm of the research. Ten women without history of autoimmune disease or pelvic pain will serve as controls.

Study subjects will undergo testing for intestinal permeability a week or more before their scheduled surgery. Both controls and pain patients will be tested for permeability using a lactulose:mannitol (L:M) oral challenge. Each subject will ingest an oral preparation of Lactulose 5 gm, Mannitol 1gm and water. This preparation is available as a test kit through Genova Diagnostics labs. Erlanger Hospital lab does not have a test for measuring urinary excretion of L:M, or other method of assessing intestinal permeability.

Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio \>0.10 is consistent with increased intestinal permeability. Normally the gut does not absorb lactulose unless permeability is present. NSAIDS and alcohol increase intestinal permeability; therefore subjects will be asked to avoid the use of NSAIDS and alcoholic beverages for a week prior to the test.

Following the L:M testing, the patients who have been enrolled will undergo surgery as planned. The surgeons should be blinded to the results of the L:M testing until after the surgery. It is assumed that some of the patients will have surgical evidence of endometriosis and some will not. The ultimate categories for analysis will be 1) Pain with biopsy proven endometriosis, and surgical staging of disease, 2) Pain without surgical evidence of endometriosis, 3) Control patients with no history of chronic pain, alcoholism, celiac disease or other autoimmune disease. As a secondary element of this study, correlation to the presence of interstitial cystitis (IC) will also be assessed as all patients in our practice who undergo surgical evaluation for chronic pain simultaneously are evaluated for IC by cystoscopy with hydrodistention.

Data that the investigators will gather includes: demographic, pelvic pain parameters, information on use of tobacco and alcohol, medical history to exclude autoimmune disease patients and patients with diabetes, intestinal permeability test results and date of test, surgical findings, American Society of Reproductive Medicine, ASRM, Endometriosis staging when applicable, presence of extrapelvic endometriosis, pathology results and presence or absence of interstitial cystitis.

Because this is an unexplored area of research, preliminary data to demonstrate potential efficacy before embarking on a prospective trial is essential.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2017-02-01
• Study First Submitted QC: 2017-02-01
• Study First Posted: 2017-02-03
• Primary Completion: 2019-06
• Study Completion: 2019-06
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-27
• Last Update Posted: 2020-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 46

Inclusion Criteria

• Female patients with documented history of pelvic pain for the study arm.
• Healthy female controls without history consistent with autoimmune disease or pelvic pain

Exclusion Criteria

• Co-morbid autoimmune disease such as Celiac disease, lupus, ankylosing spondylitis, alcoholism and diabetes which have been shown to exhibit elevated levels of Zonulin and therefore impaired intestinal permeability. Drinking alcohol and taking NSAIDS elevate intestinal permeability and would affect data.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
lactulose:mannitol (L:M) oral challenge	6 hrs	Urine is collected over six hours and is then measured for ratio of L:M. An L:M ratio \>0.10 is consistent with increased intestinal permeability. Normally the gut does not absorb lactulose unless permeability is present.

Secondary Outcome Measures

Name	Time	Method
Surgical Findings	24 hrs	Pathology reported-- endometriosis or no endometriosis

Trial Locations

Locations (2)

Erlanger Medical Center; 🇺🇸 Chattanooga, Tennessee, United States

Women's Surgery Center; 🇺🇸 Chattanooga, Tennessee, United States