Intestinal Permeability and Endometriosis

Endometriosis Clinical Trial

Official title:

Intestinal Permeability and Endometriosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03042923
• Other study ID #: 16-029
• Status: Completed
• Start date: April 2016
• Est. completion date: June 2019

Study information

• Verified date: April 2020
• Source: University of Tennessee
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• lactulose:mannitol (L:M) oral challenge

Locations

Country	Name	City	State
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Women's Surgery Center	Chattanooga	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
University of Tennessee

Country where clinical trial is conducted

United States, 

References & Publications (6)

Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995 May;108(5):1566-81. Review. — View Citation

Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012 Sep;11(11):806-14. doi: 10.1016/j.autrev.2012.01.005. Epub 2012 Feb 4. Review. — View Citation

Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008 Nov;173(5):1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2. — View Citation

Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258:25-33. doi: 10.1111/j.1749-6632.2012.06538.x. Review. — View Citation

Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. Epub 2005 Feb 14. — View Citation

WITEBSKY E, ROSE NR, TERPLAN K, PAINE JR, EGAN RW. Chronic thyroiditis and autoimmunization. J Am Med Assoc. 1957 Jul 27;164(13):1439-47. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lactulose:mannitol (L:M) oral challenge	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.	6 hrs
Secondary	Surgical Findings	Pathology reported-- endometriosis or no endometriosis	24 hrs