Gender Disparity and Hormones in Cystic Fibrosis

The objective of this study is to investigate the impact of hormones on lung disease in Cystic Fibrosis (CF) patients. Due to improved therapies, CF patients are living longer and healthier lives than they did 20 years ago. However, females have been shown to have a survival disadvantage. The median life expectancy is 33 in women and 37 in men with CF. The hypothesis is that estrogen and/or progesterone negatively impact lung health in CF. Therefore, understanding the impact of sex hormones (including the use of birth control pills) on the disease process is increasingly important. The purpose of this study is to determine if lung function, respiratory symptoms, or various markers of lung health change during different phases of the natural ovulatory cycle in order to understand if estrogen or progesterone hormones are impacting the disease relative to fluctuations in men with stable testosterone levels. The research objectives of this project are to:

• Determine if lung function, respiratory symptoms, or various markers of lung health change during different hormonal phases of the ovulatory cycle in women.
• Determine if men change lung function, respiratory symptoms, or various markers of lung health over time.
• Determine if oral contraceptive pills in women stabilize fluctuations in symptoms and improve lung health.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis (CF)
• Intervention / Treatment: Drug: Loestrin (norethindrone acetate and ethinyl estradiol)

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75207
      • Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female cystic fibrosis patients
• Must be greater than or equal to 18 years of age.
• All subjects must understand and sign the informed consent.
• Subjects must have the ability to read and write in English.
• Female subjects starting this study must be willing to use a double barrier method of birth control (such as condom or diaphragm) used with a spermicide (a substance that kills sperm), while participating in the study.

Exclusion Criteria for Main Study:

• Women who are pregnant, breast feeding, or who have had an oophorectomy.
• Women who have received a hormone contraceptive injection (such as Depo Provera) within the last 3 months.

Exclusion Criteria for Substudy:

• Men
• Women who have a history of breast cancer, abnormal vaginal bleeding, liver disease, coronary artery disease, cerebrovascular disease, uncontrolled hypertension, diabetes mellitus with vascular disease, or have had a stroke, heart attack, or blood clot within the past year, due to a possible reaction to Loestrin.
• Women who currently smoke cigarettes, due to the increased risk of serious cardiovascular events with Loestrin use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Main study; The main study is an observational study. All women will be followed for one menstrual cycle (or approximately one month) observationally off of any hormone supplementation. They will have 3 study visits corresponding to their menstrual cycle phases (menses, ovulation, and luteal). Women participating in the main study may participate in the optional interventional sub-study. Men participating in this study will be followed for 1 month observationally. They will have 3 study visits that correlate with the female arm of this study.
Experimental: Loestrin Optional Substudy; Women participating in the main study may participate in the optional sub-study. Following a negative urine pregnancy test, women will be started on once daily oral Loestrin (1.5 mg norethindrone + 0.03 mg ethyl estradiol). They will be followed for two months on this agent and have 2 additional study visits.	Drug: Loestrin (norethindrone acetate and ethinyl estradiol); This is an optional substudy that females participating in the main study can choose to participate in. Loestrin, an oral contraceptive or birth control pill, will be prescribed and taken daily for approximately 2 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in percent predicted forced expiratory volume in 1 second (FEV1)	Through Visit 5, if applicable (or approximately 3 months)

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Raksha Jain, MD, MSCI, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: December 26, 2013
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (Estimate): January 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 27, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Hormone; Loestrin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Sequential; Estradiol; Ethinyl Estradiol; Norethindrone; Norethindrone Acetate; Norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination
• Other Study ID Numbers: STU 072013-079

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No