Prostaglandin E2 as a Critical Mediator of Sex Disparities in Asthma

This study seeks to understand how biological sex influences airway hyperresponsiveness in adult asthma.

Study Overview

• Status: Withdrawn
• Conditions: Asthma
• Intervention / Treatment: Diagnostic test: Methacholine challenge; Diagnostic test: Mannitol challenge

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Asthmatics at VUMC

Description

Inclusion Criteria:

• Subject must be able to understand and provide informed consent
• Age 18-50
• A history of physician-diagnosed asthma well controlled as assessed by ACQ-6 <1.5 and FEV1>70% of predicted and FEV1 >1.5 liters.
• Asthma must be persistent, defined by the requirement of a daily controller agent.
• Use of a stable dose of daily inhaled corticosteroids for the prior 3 months.
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry and at each study visit.

Exclusion Criteria:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• Hypogonadism, irregular menstrual cycles, polycystic ovarian syndrome (PCOS), exogenous hormonal supplements or contraception.
• Any chronic lung condition outside of asthma including chronic obstructive pulmonary disease (COPD), interstitial lung disease, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis.
• Inability or unwillingness to hold the following medications prior to mannitol and methacholine inhalational challenge(s): Short-Acting Beta 2 Agonists >8 hours, Inhaled Corticosteroids and Anticholinergic Bronchodilators >12 hours, Phosphodiesterase Inhibitors or Adenosine Receptors >24 hours, Long-acting Beta 2 Agonists >36 hours, Long-acting Anticholinergics or Short-Acting Antihistamines >48 hours, Long-Acting Antihistamines >72 hours, and Leukotriene-Receptor Antagonist or 5-Lipooxygenase Inhibitors >4 days.
• For males, a screening morning serum total testosterone level (obtained between 8-10 AM) below the normal reference lab value.
• Current pregnancy, breast-feeding, or plans to become pregnant during the study period.
• Oral or systemic corticosteroid use or biologic agent for asthma in the previous 3 months or ED/Hospitalization for asthma within 6 months.
• Use of investigational drugs within 12 weeks of participation.
• Known hypersensitivity or allergy to mannitol, gelatin or methacholine.
• Upper or lower respiratory tract infection within the proceeding 6 weeks.
• A history of uncontrolled hypertension, coronary artery disease, stroke, epilepsy, urinary tract obstruction, untreated thyroid disease, or a chronic lung disease other than asthma.
• Daily use of a beta-blocker.
• Intolerance to anticholinergic medications.
• Inability to produce an adequate sputum sample.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Males with asthma; Induced sputum, methacholine challenge, and mannitol challenge will be performed.	Diagnostic test: Methacholine challenge; Methacholine inhalation challenge will be administered to both male and females with asthma; Diagnostic test: Mannitol challenge; Mannitol inhalation challenge will be administered to both male and females with asthma
Females with asthma; Induced sputum, methacholine challenge, and mannitol challenge will be performed.	Diagnostic test: Methacholine challenge; Methacholine inhalation challenge will be administered to both male and females with asthma; Diagnostic test: Mannitol challenge; Mannitol inhalation challenge will be administered to both male and females with asthma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Provacative dose of mannitol that elicits a 15% decline in forced expiratory volume in males	Males only	Baseline
Provacative dose of mannitol that elicits a 15% decline in forced expiratory volume in females	Females only during the luteal phase of the menstrual cycle	Baseline

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2021
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (ACTUAL): January 31, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Cholinergic Agonists; Respiratory System Agents; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Mannitol; Methacholine Chloride
• Other Study ID Numbers: PGE2 in asthma

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No