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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by The Hospital for Sick Children.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00700050
First received: June 16, 2008
Last updated: June 17, 2008
Last verified: June 2008
History of Changes
  Purpose

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 Intervention Phase
Cystic Fibrosis
 Drug: Hypertonic saline
 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Modulation by Sex Hormones of Inflammation and Susceptibility to Pseudomonas Aeruginosa in Cystic Fibrosis Airways - A Pilot Study

Resource links provided by NLM:

MedlinePlus related topics: Cystic Fibrosis
U.S. FDA Resources

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: April 2008
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Hypertonic saline
The subjects in this arm will be those from Group 1 (females with cystic fibrosis). They will be asked to inhale up to 2 puffs of salbutamol via Metered Dose Inhaler. Briefly, after the subject has performed post-bronchodilator spirometry, she will inhale increasing concentrations of 3, 4 and 5% of hypertonic saline for 7 minutes each for 3 cycles until expectorating a sufficient sputum sample.
Active Comparator: 2 Drug: Hypertonic saline
The subjects in this arm will be those from Group 2 (females without cystic fibrosis). They will be asked to inhale up to 2 puffs of salbutamol via Metered Dose Inhaler. Briefly, after the subject has performed post-bronchodilator spirometry, she will inhale increasing concentrations of 3, 4 and 5% of hypertonic saline for 7 minutes each for 3 cycles until expectorating a sufficient sputum sample.
Active Comparator: 3 Drug: Hypertonic saline
The subjects in this arm will be those from Group 3 (males with cystic fibrosis). They will be asked to inhale up to 2 puffs of salbutamol via Metered Dose Inhaler. Briefly, after the subject has performed post-bronchodilator spirometry, he will inhale increasing concentrations of 3, 4 and 5% of hypertonic saline for 7 minutes each for 3 cycles until expectorating a sufficient sputum sample.
Active Comparator: 4 Drug: Hypertonic saline
The subjects in this arm will be those from Group 4 (males without cystic fibrosis). They will be asked to inhale up to 2 puffs of salbutamol via Metered Dose Inhaler. Briefly, after the subject has performed post-bronchodilator spirometry, he will inhale increasing concentrations of 3, 4 and 5% of hypertonic saline for 7 minutes each for 3 cycles until expectorating a sufficient sputum sample.

Detailed Description:

Most CF patients die because of chronic lung infection with Ps aer, 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 AMPs, responsive to sex hormone in the CF human respiratory tract, including one (LTF) with known activity against Ps aer biofilm formation. Our preliminary results show additive activity of LTF and STH against Ps aer biofilm formation, and that LTF and STH also inhibit attachment of Ps aer 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. Confirmation of our current hypotheses will position us for future testing of the capacity of progesterone and estrogen antagonists, androgen agonists and the three specific AMPs, to inhibit inflammation and / or infection in available animal models of CF.

  Eligibility

Ages Eligible for Study:   up to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

GROUP 1 (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)
  • 22 years of age or younger
  • 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
  • Pancreatic insufficient
  • Able to give consent on her own behalf

GROUP 2 (FEMALES WITHOUT CF)

  • Sexually mature females
  • 22 years of age or younger
  • Have regular, normal menses
  • Able to give consent on her own behalf

GROUP 3 (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)
  • 22 years of age or younger
  • 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

GROUP 4 (MALES WITHOUT CF)

  • Sexually mature males
  • 22 years of age or younger
  • 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 significant nasal atopy or polyps
  • Has used systemic or nasal corticosteroids within the preceding two weeks
  • Has nasal trauma
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00700050

Locations
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada
Contact: Neil Sweezey, MD     416-813-5128     neil.sweezey@sickkids.ca    
Principal Investigator: Neil Sweezey, MD            
Sub-Investigator: Mustafa Osman, MD            
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Neil Sweezey, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Neil Sweezey/Principal Investigator, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00700050     History of Changes
Other Study ID Numbers: 1000011620
Study First Received: June 16, 2008
Last Updated: June 17, 2008
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
Cystic Fibrosis
Sex hormones
Pseudomonas aeruginosa
Paediatrics

Additional relevant MeSH terms:
Cystic Fibrosis
Disease Susceptibility
Genetic Predisposition to Disease
Fibrosis
Inflammation
Pseudomonas Infections
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Infant, Newborn, Diseases
Disease Attributes
Pathologic Processes
Gram-Negative Bacterial Infections
Bacterial Infections
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013