Vascular Function and Uterine Fibroids

Sympathetic Nerve Activity and Vascular Function in Women With Uterine Leiomyomata

The purpose of this study is to learn how uterine fibroids may be connected to heart disease and high blood pressure. It is not known what causes fibroids, but they frequently occur in women who also have high blood pressure, heart disease, and stroke. The investigators of this study want to learn if certain changes in the blood vessels or nerve activity can put women at risk for these diseases and for fibroids.

Study Overview

• Status: Completed
• Conditions: Leiomyoma
• Intervention / Treatment: Device: Brachial artery catheter; Drug: Acetylcholine; Drug: Nitroprusside; Drug: Norepinephrine; Drug: Nitroprusside and phenylephrine

Detailed Description

The investigators are inviting women, 25-50 years old, who have not gone through menopause to participate in this study. The investigators are looking for some women with uterine fibroids and some without uterine fibroids based on ultrasound or MRI. If the patients have not had a recent ultrasound or MRI of the uterus, a physician can provide one.

Individuals cannot participate if they have high blood pressure, diabetes, or disease in the kidneys, lungs, or blood vessels. Also, individuals who smoke, have high cholesterol, or are obese (BMI is higher than 30) cannot participate. Certain medications, including high blood pressure medications, beta-blockers and anti-depressants, will also limit potential patient participation. The investigators would be happy to review medications for potential participants.

Screen Day:

One of the members of the research team will review the study and the informed consent document with the patient. The patient will have their height, weight, blood pressure, pulse and respirations measured. The patient will also complete three questionnaires. If the patient has not had an ultrasound of the uterus in the last 12 months, a physician will complete one for her.

Study Day:

The patient will need to fast overnight (no eating or drinking). The investigators will draw a blood sample and then do a series of tests on the participant's blood vessels. For some of the tests, medication will be given through an IV. The investigators will also test nerve activity in the nerve on the outer aspect of the leg.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Premenopausal women, ages 25-50 years old, who have and have not been diagnosed with uterine fibroids. Women will be recruited from Rochester, Minnesota and the surrounding area (including locations in Iowa and Wisconsin). Women eligible to participate will be in good health and not taking medications.

Description

Inclusion Criteria:

• Women 25-50 years old
• Premenopausal

Exclusion Criteria:

• Postmenopausal
• Pregnant or currently breastfeeding
• Using blood pressure medications or anti-depression medications
• High blood pressure
• Diabetes
• Disease in the kidneys, lungs, or blood vessels
• Chronic diseases (for example: Crohn's disease, rheumatoid arthritis, bipolar mood disorder, etc.)
• Smoker
• High cholesterol
• BMI higher than 30

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with uterine fibroids; Brachial artery catheter; Acetylcholine; Nitroprusside; Norepinephrine; Nitroprusside and phenylephrine	Device: Brachial artery catheter; A catheter will be placed in the brachial artery by a physician on the study day.; Drug: Acetylcholine; Acetylcholine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Acetylcholine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Nitroprusside; Nitroprusside will be infused into the brachial catheter while blood flow levels in the forearm are measured. Nitroprusside will be infused at the following doses: 0.25, 0.5, 1.0, and 2.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Norepinephrine; Norepinephrine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Norepinephrine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Nitroprusside and phenylephrine; A single dose of nitroprusside (100 ug) will be infused through an IV; one minute later, a single dose of phenylephrine (150 ug) will be infused.
Women without uterine fibroids; Brachial artery catheter; Acetylcholine; Nitroprusside; Norepinephrine; Nitroprusside and phenylephrine	Device: Brachial artery catheter; A catheter will be placed in the brachial artery by a physician on the study day.; Drug: Acetylcholine; Acetylcholine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Acetylcholine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Nitroprusside; Nitroprusside will be infused into the brachial catheter while blood flow levels in the forearm are measured. Nitroprusside will be infused at the following doses: 0.25, 0.5, 1.0, and 2.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Norepinephrine; Norepinephrine will be infused into the brachial catheter while blood flow levels in the forearm are measured. Norepinephrine will be infused at the following doses: 1.0, 2.0, 4.0, and 8.0 ug/100 ml tissue/min for 2 minutes each.; Drug: Nitroprusside and phenylephrine; A single dose of nitroprusside (100 ug) will be infused through an IV; one minute later, a single dose of phenylephrine (150 ug) will be infused.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline systolic, diastolic, and mean blood pressures		One day (study day)
Baseline sympathetic nerve activity	Nerve "burst" activity will be measured across 10 minutes.	One day (study day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in forearm blood flow levels in response to acetylcholine infusion		One day (study day)
Changes in forearm blood flow levels in response to nitroprusside infusion		One day (study day)
Changes in forearm blood flow levels in response to norepinephrine infusion		One day (study day)
Change in blood pressure in response to infusions of nitroprusside and phenylephrine	An infusion of nitroprusside will be given, followed by an infusion of phenylephrine one minute later.	One day (study)
Pulse wave velocity (an index of vessel stiffness)		One day (study day)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Female sex hormone levels	Blood samples will be collected to measure levels of estrogen and progesterone.	One day (study day)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael J Joyner, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: April 16, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (Estimate): April 25, 2014

Study Record Updates

• Last Update Posted (Actual): March 2, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Blood pressure; Autonomic nervous system; Vascular stiffness; Physiological effects of drugs; Blood vessels
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Cholinergic Agonists; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nitric Oxide Donors; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline; Nitroprusside; Acetylcholine
• Other Study ID Numbers: 13-000596