TransMEM Gas Exchange -- Project 1, Aim 2

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
William J. Doyle, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01925729
First received: August 8, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

This study will determine if exposure to an allergy material (ragweed) or exposure to an allergic-symptom-provoking substance (histamine) and medications typically used to decongest the nose changes the rate of blood-flow in the lining of the middle-ear. Otitis media (the build-up of water-like fluid in the middle-ear airspace) may occur if the blood flow in the lining of the middle-ear is too high and may be prevented if a way could be found to lower the blood flow in persons susceptible to the disease. Middle-ear blood flow is measured indirectly by measuring the change in middle-ear pressure while a person breathes a gas mixture containing nitrous oxide ("laughing gas"). In this study, 4 groups of subjects will be entered and middle-ear pressure in persons breathing a mixture of 50% Oxygen, 50% Nitrous Oxide ("laughing gas")will be measured after exposure to one of four substances (ragweed, histamine,an oral decongestant, a decongestant nasal spray) and a fake medication (placebo) at separate test sessions. All subjects will have one set of 2 x-rays of the middle ears and mastoids. The group exposed to ragweed will require 3 study visits while the other 3 groups will have 2 study visits. From this information middle-ear blood flow will be calculated. This will help determine the relationship between what happens in the nose and what happens in the middle ear.


Condition Intervention
Middle Ear Disease
Nasal Allergy
Biological: ragweed
Biological: histamine
Drug: pseudoephedrine
Drug: Oxymetazoline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Middle Ear Pressure Regulation in Health and Disease -- Gas Supply, Demand and Middle Ear Gas Balance -- Specific Aim 2

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • change in trans-middle ear N2O exchange constant [ Time Frame: Visit 1 and Visit 2 (Visits 2 and 3 for ragweed arm) up to approximately 3 weeks ] [ Designated as safety issue: No ]
    The transMEM N2O exchange constant is the primary outcome measure and is calculated as the slope of the line relating middle-ear pressure to time (until an observable active or passive ET opening) divided by the estimated extant N2O gradient.


Estimated Enrollment: 120
Study Start Date: October 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ragweed
ragweed -- 1000PNU intranasal spray
Biological: ragweed
ragweed arm only
Experimental: histamine
5 mg intranasal spray
Biological: histamine
histamine arm only
Experimental: pseudoephedrine
pseudoephedrine -- 60 mg orally
Drug: pseudoephedrine
pseudoephedrine arm only
Other Name: Sudafed
Experimental: oxymetazoline
oxymetazoline 0.05% solution intranasal spray
Drug: Oxymetazoline
oxymetazoline arm only
Other Name: Afrin

Detailed Description:

The set of four experiments described here is a subcomponent of one Project included in a Clinical Research Center Grant Program focused on the physiology and pathophysiology of middle-ear (ME) pressure-regulation in children and adults. These experiments are designed to measure the rate of transME mucosal (transMEM) inert gas exchange in adults and determine if nasal inflammatory reactions experimentally provoked by intranasal histamine or allergen challenge increase the rate transMEM inert gas exchange and if nasal or oral treatment with an adrenergic agonist decreases that rate. Four cohorts of 20 otherwise healthy adults will be identified and one cohort assigned to each of the four experiments. All subjects will have a x-ray in Schuller projection to estimate mastoid volume. The transMEM inert gas exchange rate is measured by repeatedly recording ME pressure by tympanometry while the subject breathes a mixture of 50%N2O/ 50%O2, and then regressing ME pressure on time and dividing the slope of the function by the estimated N2O driving gradient to yield an exchange constant. For each experiment, the transMEM N2O exchange rate is measured twice at separate visits (active and placebo). The four experimental conditions are: (1) intranasal ragweed and placebo challenges; (2) intranasal histamine and placebo challenges; (3) oral pseudoephedrine and placebo; (4) intranasal oxymetazoline and placebo. Experiments 2-4 require two visits, while Experiment 1 will require an additional visit to obtain blood for RAST testing to verify ragweed allergy. The paired exchange constants measured in each experiment will be compared for a significant difference using a Student's Paired t test and the results interpreted as supporting or refuting the possibility of modulating the transMEM N2O exchange rate by the different procedures.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy
  • no evidence of otitis media at entry
  • bilaterally intact tympanic membranes
  • ragweed arm: history of symptomatic ragweed allergy and Class 2 positive on RAST testing with or without other allergic sensitivities by history

Exclusion Criteria:

  • craniofacial syndrome (ef, cleft palate)
  • Use of prescription medications (except for birth control) in the 1 month prior to entry;
  • Use of over-the-counter allergy medication within 2 weeks before challenge (Experiments 1, 2 only);
  • Use of over-the-counter decongestants (nasal or oral) within 2 weeks before challenge (Exp 3,4 only)
  • Elevated blood pressure (>140/90);
  • Individuals with any pulmonary or cardiac problems, including asthma;
  • Individuals who are pregnant or who are planning to become pregnant during the period of study;
  • Individuals who had immunotherapy for ragweed allergy at any time (Experiment 1 only);
  • Individuals who used any experimental medication or treatment within 3 months of screening;
  • Individuals with extant unilateral or bilateral otitis media as documented by otoscopy or tympanometry;
  • Individuals with abnormally low tympanic membrane mobility, eg Type B tympanogram;
  • Individuals reporting a previous adverse experience with breathing gas mixtures containing N2O (e.g. during dental procedures);
  • Individuals who have upper respiratory ("cold") symptoms or allergic rhinitis symptoms (may be rescheduled);
  • Individuals with single or multiple allergic sensitivities by screening history (Experiment 2 only)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925729

Contacts
Contact: Julianne Banks 412-692-3595
Contact: Jenna El-Wagaa 412-692-3595

Locations
United States, Pennsylvania
Middle Ear Physiology Laboratory, University of PIttsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: William J Doyle, PhD         
Sub-Investigator: Cuneyt M Alper, MD         
Sub-Investigator: Douglas Swarts, PhD         
Sub-Investigator: Ellen M Mandel, MD         
Sub-Investigator: Miriam S Teixeira, MD, PhD         
Sub-Investigator: Brian Martin, DMD         
Sub-Investigator: Todd Green, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: William J Doyle, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: William J. Doyle, Professor of Otolaryngology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01925729     History of Changes
Other Study ID Numbers: PRO13040386, 2P50DC007667-07
Study First Received: August 8, 2013
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
middle ear
allergy
nose

Additional relevant MeSH terms:
Ear Diseases
Immune System Diseases
Otorhinolaryngologic Diseases
Hypersensitivity
Pseudoephedrine
Oxymetazoline
Phenylephrine
Ephedrine
Histamine
Histamine phosphate
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Respiratory System Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Central Nervous System Stimulants
Central Nervous System Agents
Sympathomimetics
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Histamine Agonists
Histamine Agents
Adrenergic alpha-Agonists

ClinicalTrials.gov processed this record on July 24, 2014