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

Sponsor
The Hospital for Sick Children (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00700050
Collaborator
Unity Health Toronto (Other)
80
1
176
0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Hypertonic saline
  • Drug: Hypertonic saline
  • Drug: Hypertonic saline
  • Drug: Hypertonic saline

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 Design

Study Type:
Observational
Anticipated Enrollment :
80 participants
Observational Model:
Case-Control
Time Perspective:
Cross-Sectional
Official Title:
Modulation by Sex Hormones of Inflammation and Susceptibility to Pseudomonas Aeruginosa in Cystic Fibrosis Airways - A Pilot Study
Actual Study Start Date :
Apr 1, 2008
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm 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
  • Outcome Measures

    Primary Outcome Measures

    1. 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 [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.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    14 Years to 28 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Hospital for Sick Children Toronto Ontario Canada

    Sponsors and Collaborators

    • The Hospital for Sick Children
    • Unity Health Toronto

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Neil Sweezey, Staff Respirologist, The Hospital for Sick Children
    ClinicalTrials.gov Identifier:
    NCT00700050
    Other Study ID Numbers:
    • 1000011620
    First Posted:
    Jun 18, 2008
    Last Update Posted:
    Mar 1, 2021
    Last Verified:
    Feb 1, 2021
    Keywords provided by Neil Sweezey, Staff Respirologist, The Hospital for Sick Children
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 1, 2021