Completed

MAROMediators of Abnormal Reproductive Function in Obesity

0 criteria met from your profileSee at a glance how your profile meets each eligibility criteria.
What is being tested

Microdialysis

+ Vascepa - Fish Oil

+ Aspirin

OtherDietary SupplementDrug
Who is being recruted

Urogenital Diseases+12

+ Genital Diseases

+ Body Weight

From 18 to 60 Years
See all eligibility criteria
How is the trial designed

Basic Science Study

Early Phase 1
Interventional
Study Start: March 2013
See protocol details

Summary

Principal SponsorUniversity of Colorado, Denver
Last updated: March 17, 2015
Sourced from a government-validated database.Claim as a partner

Study start date: March 1, 2013

Actual date on which the first participant was enrolled.

Specific Aim 1: To determine whether aromatase activity is measurable in adipose tissue using the 'compound' (see appendix) as a precursor and whether aromatase is decreased in the adipose tissue of obese women, and whether this varies by regional fat location. The investigators will accomplish this by examining precursor/product ratios of hormones infused through microdialysis using the 'compound' as a substrate. Hypothesis for specific aim 1: Aromatase activity will be measurable in adipose tissue using testosterone as a precursor. Estradiol, but not estrone production from androgen precursors will be decreased in obese women relative to those of normal weight. Specific Aim 2: To determine whether nonspecific, systemic suppression of inflammation will lead to improved reproductive hormonal profiles of luteinizing hormone (LH), follicle stimulating hormone(FSH), Estrone conjugates (E1c) and pregnandiol glucuronide (Pdg) in obese women who undergo two menstrual cycles of study: one off treatment and one on treatment. This aim shall be accomplished by performing daily urinary hormone monitoring of two menstrual cycles, one prior to and one during treatment with low-dose aspirin and polyunsaturated fatty acids (PUFAs). Hypothesis for specific aim 2: A nonspecific, systemic inflammatory suppression therapy will result in improved urinary profiles of LH, FSH, E1c and Pdg. Specific Aim 3: To determine whether 4 weeks of reduction of circulating insulin will result in improved reproductive hormonal profiles of LH, FSH, Estrone conjugates (E1c) and pregnandiol glucuronide (Pdg) in obese women who undergo two menstrual cycles of study: one off treatment and one on treatment. This aim shall be accomplished by performing daily urinary hormone monitoring of two menstrual cycles, one prior to and one during treatment with pioglitazone. Hypothesis for specific aim 3: Chronic lowering of insulin with pioglitazone treatment of obese women will result in improved urinary profiles of LH, FSH, E1c and Pdg.

NCT01817400
Principal SponsorUniversity of Colorado, Denver
Last updated: March 17, 2015
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

10 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Basic Science Study

Basic science studies help researchers understand how the body works or how a disease develops. They don't test treatments, but they build the foundation for future therapies.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Female

Biological sex of participants that are eligible to enroll.

From 18 to 60 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Urogenital DiseasesGenital DiseasesBody WeightFemale Urogenital Diseases and Pregnancy ComplicationsGenital Diseases, FemaleInfertilityNutrition DisordersNutritional and Metabolic DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsOvernutritionOverweightFemale Urogenital DiseasesInfertility, FemaleObesity

Criteria

Inclusion Criteria: Women aged 18-39* who meet the following criteria will be enrolled: *Women age 40-60 can be enrolled in Group A BMI at least 30 kg/m2 (Groups B and C only) No history of chronic disease affecting hormone production, metabolism or clearance No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin) No use of reproductive hormones within 3 months of enrollment No medical conditions that are known to affect urinary hormone excretion or that may interfere with urinary hormone measurement (Groups B and C only) No history of or active bladder cancer (Group C only, since pioglitazone is contraindicated in individuals with bladder cancer) Normal prolactin and thyroid stimulating hormone levels at screening History of regular menstrual cycles every 25-40 days Use of a reliable method of contraception (female or male partner sterilization; intrauterine device (IUD); abstinence; diaphragm) Hemoglobin A1c <6% Exclusion Criteria: Women aged 18-39* who meet the following criteria will be enrolled: *Women age 40-60 can be enrolled in Group A BMI at least 30 kg/m2 (Groups B and C only) No history of chronic disease affecting hormone production, metabolism or clearance No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin) No use of reproductive hormones within 3 months of enrollment No medical conditions that are known to affect urinary hormone excretion or that may interfere with urinary hormone measurement (Groups B and C only) No history of or active bladder cancer (Group C only, since pioglitazone is contraindicated in individuals with bladder cancer) Normal prolactin and thyroid stimulating hormone levels at screening History of regular menstrual cycles every 25-40 days Use of a reliable method of contraception (female or male partner sterilization; IUD; abstinence; diaphragm) Hemoglobin A1c <6%

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

3 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
Microdialysis probes will be inserted into the abdominal and femoral subcutaneous adipose tissue. Two "control" probes at each site will be perfused at 2.0 µL/min with Ringer's solution to measure basal interstitial testosterone and estradiol levels. One "experimental" probe at each site will be perfused with the 'compound' 20ug/dl at 2.0 µL/min to assess the interstitial conversion of androstenedione to estrone and estradiol. The 'compound' will be infused. Either one or the other hormone (androstenedione OR testosterone) will be used per experiment. The second "control" probe will be positioned at each site to ensure acquisition of data in the event that one of the other probes becomes dysfunctional. We will then collect microdialysis samples every 60 min over the next 120 min.

Group II

Experimental
We will perform a control cycle of daily, first-morning voided urine, as previously reported by our group to assess the hormonal features of the menstrual cycle of each of the five participants in this arm. Upon completion of the control cycle, the participant will initiate therapy with aspirin 81mg per day, plus Vascepa - Fish Oil 30mg daily. Participants will collect urine for a second menstrual cycle while on treatment, using methods that we have previously employed. At the completion of the second cycle of urine collection, the medications will be stopped and the study will be completed.

Group III

Experimental
We will perform a control cycle of daily, first morning voided urine as previously reported by our group, to assess the hormonal features of the menstrual cycle of each of the five participants. Upon completion of the control cycle, the participant will initiate therapy with pioglitazone, 45 mg daily, a dose that has previously been shown to result in a 30% reduction in fasting insulin. She will take the pioglitazone without any monitoring for a second menstrual cycle and then collect urinary hormones for the third menstrual cycle, continuing the pioglitazone until the third menstrual cycle is completed.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

University of Colorado Denver Anschutz Medical Campus

Aurora, United StatesOpen University of Colorado Denver Anschutz Medical Campus in Google Maps
CompletedOne Study Center