Clinical trial NCT01184144: Endometriosis: Immunomodulation
Official title: Effect of Pioglitazone on Peritoneal Cytokines in Women With Endometriosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Endometriosis
Keywords: Endometriosis
Peritoneal fluid
Cytokines
Peroxisome Proliferator-Activated Receptors
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2010-08-18
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to compare the effect of pioglitazone versus no drug on soluble profinflammatory markers in peritoneal fluid of women with endometriosis.

Detailed description: The overall goal of this proposal is to assess modulation of immune mechanisms in endometriosis. Endometriosis is a common ailment affecting approximately five million reproductive-aged American women. We will test the efficacy of a novel immunomodulatory drug (peroxisome proliferator activated receptor gamma, PPAR-gamma, agonist), pioglitazone, to reduce peritoneal fluid cytokine concentrations in women with endometriosis compared with the non-treated controls (randomized controlled trial). Based on prior studies done by the investigator highlighting the major role of cytokines and the immune system in the genesis or propagation of endometriosis, these experiments could lead to improved translational treatment strategies and a better understanding of endometriosis. Acting through PPAR-gamma, TZDs inhibit proinflammatory cytokines as well as NF-kB, an important nuclear transcription factor for the production of many cytokines. Accordingly, since human endometrial epithelial and stromal cells contain PPAR-gamma, we felt i would be useful to evaluate the influence of a PPAR-gamma ligand, pioglitazone, on the concentration of specific peritoneal fluid cytokines.

Comparison: After the pre-trial screening, eligible subjects with presumed endometriosis and age 18-45 will be consented and randomly assigned to receive either pioglitazone (30 mg, daily)or no drug for 2 weeks. Peritoneal fluid will be collected at the time of surgery and the volume measured. All patients enrolled in the study will have their surgery during the follicular phase of the cycle in order to minimize differences in volume and cytokine concentration due to the cyclical changes. The primary measure will be the peritoneal fluid concentration comparisons of the two groups assessing six different cytokines.

Eligibility criteria: Inclusion Criteria:

1. Healthy woman age 18 - 45 years.
2. Regular cycles (24-35 days).
3. Pelvic pain ≥ 3 months.
4. Negative pregnancy test.
5. Non-lactating.
6. No prior (\<3 months) use of hormonal therapy.
7. No history of liver disease.
8. Suspected endometriosis and scheduled for surgery to confirm this diagnosis
9. Surgery scheduled in follicular phase.
10. Consent to participate in the study.
11. Enrollment into data analysis portion of study if:

    * Endometriosis diagnosed from surgical specimen by routine hematoxylin and eosin staining and histological evaluation.

Exclusion Criteria:

1. Major psychiatric conditions or the abuse of alcohol or drugs which would make it difficult for the subject to complete study procedures.
2. Active or prior infection with hepatitis, human immunodeficiency virus (HIV) infection, or history of high-risk activities (e.g., IV drug abuse) which would increase risk to laboratory personnel. Of note, no testing for hepatitis or HIV will be performed as part of this study and all tissues will be handled and discarded as if they were potentially infected.
3. Patients with liver dysfunction (elevated liver enzymes \> 2 times the upper limit of normal).
4. Presence of pre-existing malignancy, including carcinoma of the breast or uterus.
5. Women with other causes of chronic pelvic pain including infectious, gastrointestinal, musculoskeletal, neurologic or psychiatric.
6. Elevated WBC.
7. NYHA functional class I-IV heart failure.
8. Diabetes mellitus.
9. Known pregnancy or positive pregnancy test.

Primary outcomes:
measure: Peritoneal cytokine levels
timeFrame: Within 1 year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Univ Wisconsin
name: Dan I Lebovic, MD
role: PRINCIPAL_INVESTIGATOR
References: