Modulation by Sex Hormones of Inflammation and Susceptibility to Pseudomonas Aeruginosa in Cystic Fibrosis Airways

February 25, 2021 updated by: Neil Sweezey, The Hospital for Sick Children

Modulation by Sex Hormones of Inflammation and Susceptibility to Pseudomonas Aeruginosa in Cystic Fibrosis Airways - A Pilot Study

The general objective is to elucidate the mechanisms whereby sex hormones may modulate the severity of respiratory disease. An important component of this proposal is a systematic and intensive approach to characterize how the cellular and cytokine components of airway inflammation respond to fluctuations in sex hormone levels.

The effects of menstrual fluctuations in levels of sex hormones on inflammation and bacterial load in respiratory secretions of CF patients will also be determined.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Most CF patients die because of chronic lung infection with P. aeruginosa, chronic inflammation and progressive airway damage. Agents that reduce inflammation or enhance airway antibacterial defences hold potential therapeutic value. Therefore, there is considerable current interest in identifying and stimulating the activities of these agents. Although sex hormones are generally acknowledged to modulate respiratory inflammation, the downstream mechanism of such action remains incompletely understood.

We have identified three antimicrobial peptides (AMPs), responsive to sex hormone in the CF human respiratory tract, including one (LTF) with known activity against P. aeruginosa biofilm formation. Our preliminary results show additive activity of LTF and STH against P. aeruginosa biofilm formation, and that LTF and STH also inhibit attachment of P. aeruginosa to airway epithelial cells. Taken together, these findings are consistent with the concept that female sex hormones exert their negative effect on the CF lung, in part, by reducing the levels of these AMPs in the airway. The next step is to determine if female sex hormones alter airway inflammation and infection or AMP levels in the respiratory secretions of CF patients.

Study Type

Observational

Enrollment (Anticipated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • The Hospital For Sick Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 26 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The primary study population are sexually mature cystic fibrosis (CF) females with regular natural menstrual cycles. For some measurements, they serve as their own controls. For other measurements, there are up to three control groups: non-CF females, CF males and non-CF males.

Description

Inclusion Criteria:

FEMALES WITH CF

  • Sexually mature female CF patients followed at the Toronto CF Clinics of The Hospital for Sick Children (adolescents) or St. Michael's Hospital (adults)
  • 14-28 years of age
  • Diagnosis of CF is based on a typical clinical picture and confirmed by repeated sweat chloride values > 60 mEq/L as determined by pilocarpine ionophoresis (minimum 100mg sweat)
  • Have regular, normal menses
  • Able to give consent on her own behalf

FEMALES WITHOUT CF

  • Sexually mature females
  • 14-28 years of age
  • Have regular, normal menses
  • Able to give consent on her own behalf

MALES WITH CF

  • Sexually mature male CF patients followed at the Toronto CF Clinics of The Hospital for Sick Children (adolescents) or St. Michael's Hospital (adults)
  • 14-28 years of age
  • Diagnosis of CF is based on a typical clinical picture and confirmed by repeated sweat chloride values > 60 mEq/L as determined by pilocarpine ionophoresis (minimum 100mg sweat)
  • Able to give consent on his own behalf

MALES WITHOUT CF

  • Sexually mature males
  • 14-28 years of age
  • Able to give consent on his own behalf

Exclusion Criteria:

  • Is a smoker
  • Has had an upper respiratory tract infection within the preceding two weeks
  • Is taking systemic oral contraceptive therapy
  • Is pregnant
  • Has used furosemide or amiloride or had a pulmonary exacerbation in the previous month (Acute exacerbations are defined as 3 or more of the following symptoms or signs: increased cough, change in volume, colour or thickness of the sputum, fever, hemoptysis, increased shortness of breath, change in their chest radiograph or a fall in pulmonary function (FEV1) of >10% from baseline)
  • Unable to give consent on his/her own behalf

Study Plan

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

How is the study designed?

Design Details

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
CF Females
CF females, 14 - 28 years old, sexually mature, with regular menstrual cycles, not on contraceptive Pill. No intervention is being tested - subjects studied with normal menstrual variations in serum hormone levels. Hypertonic saline may be used to induce sputum production by subjects who are otherwise unable to produce a satisfactory sputum sample.
Drug: Hypertonic saline
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Other Names:
  • Sodium chloride, inhalation
Non-CF Females
Non-CF control females, 14 - 28 years old, sexually mature, with regular menstrual cycles, not on contraceptive Pill. No intervention is being tested - subjects studied with normal menstrual variations in serum hormone levels. Hypertonic saline may be used to induce sputum production by subjects who are otherwise unable to produce a satisfactory sputum sample.
Drug: Hypertonic saline
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Other Names:
  • Sodium chloride, inhalation
CF Males
CF males, 14 - 28 years old. No intervention is being tested. Hypertonic saline may be used to induce sputum production by subjects who are otherwise unable to produce a satisfactory sputum sample.
Drug: Hypertonic saline
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Other Names:
  • Sodium chloride, inhalation
Non-CF males
Non-CF control males, 14 - 28 years old. No intervention is being tested. Hypertonic saline may be used to induce sputum production by subjects who are otherwise unable to produce a satisfactory sputum sample.
Drug: Hypertonic saline
Subjects will be asked to expectorate sputum samples. If necessary to achieve this, subjects will inhale wet-nebulized 3% saline for up to 7 minutes each for up to 3 cycles.
Other Names:
  • Sodium chloride, inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Presence of inflammatory markers (cytokines, white blood cells), levels of LTF, STH and PIP. Serum levels of estrogen (E), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) will be determined in female human subjects
Time Frame: For the female patients the visits will be timed so that one measure is taken in the luteal phase of their menstrual cycle and the other is taken during the follicular phase. Male patients will be asked to come to measure these levels two weeks apart.
For the female patients the visits will be timed so that one measure is taken in the luteal phase of their menstrual cycle and the other is taken during the follicular phase. Male patients will be asked to come to measure these levels two weeks apart.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Hospital for Sick Children

Collaborators

Unity Health Toronto

Investigators

  • Principal Investigator: Neil Sweezey, MD, The Hospital For Sick Children

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2008

Primary Completion (Anticipated)

July 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

June 16, 2008

First Submitted That Met QC Criteria

June 17, 2008

First Posted (Estimate)

June 18, 2008

Study Record Updates

Last Update Posted (Actual)

March 1, 2021

Last Update Submitted That Met QC Criteria

February 25, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1000011620

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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