Study to Assess the Incidence of Local Oropharyngeal and Laryngeal Adverse Effects of Advair DISKUS 250/50 Mcg BID - Full Text View

Sponsor:	Allergy & Asthma Medical Group & Research Center
Information provided by:	Allergy & Asthma Medical Group & Research Center
ClinicalTrials.gov Identifier:	NCT00235053

Purpose

This Pilot study is designed to explore the rate of local side effects of fluticasone as delivered by Advair and to determine the best outcome measure to assess these effects. This study is the initial step, and will be followed by a larger scale study.

Condition	Intervention	Phase
Asthma Candidiasis, Oral Voice Disorders	Drug: fluticasone/salmeterol DISKUS 250/50	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety Study
Official Title:	A Pilot Study to Assess the Incidence of Local Oropharyngeal and Laryngeal Adverse Effects of Advair DISKUS 250/50 Mcg BID as Assessed by the Development of Laryngitis and Oropharyngeal Candidiasis in Adults With Mild Persistent Asthma

Resource links provided by NLM:

MedlinePlus related topics: Allergy Asthma Voice Disorders Yeast Infections

Drug Information available for: Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate Advair

U.S. FDA Resources

Further study details as provided by Allergy & Asthma Medical Group & Research Center:

Primary Outcome Measures:

To determine the magnitude of change from baseline to end of study in the Voice Handicap Index (VHI) with Advair® DISKUS 250/50 mcg BID in subjects with mild persistent asthma.

Secondary Outcome Measures:

1. Voice Related Quality of Life (VRQOL)
2. Inhaled Corticosteroid Questionnaire (ICQ)
3. Reflux Symptom Index (RSI)
4. Videostroboscopy and Determination of Reflux Finding Score (RFS)
5. Voice jitter
6. Voice shimmer
7. Signal to noise ratio
8. Oropharyngeal Candida species culture
9. Oropharyngeal Candida species related symptoms
10. Oropharyngeal thrush on physical exam

Estimated Enrollment:	13
Study Start Date:	August 2005
Estimated Study Completion Date:	November 2005

Detailed Description:

Asthma is a chronic inflammatory disorder of the airways. The inflammation is associated with bronchial hyperresponsiveness, airflow obstruction, and respiratory symptoms including wheezing, coughing and chest tightness.

Inhaled corticosteroids are the most effective controller asthma medications. They are indicated for management of persistent asthma at all levels of severity. They have been documented to improve symptoms and pulmonary function and reduce exacerbations, need for quick-relief medications and airway hyperresponsiveness.

Despite their benefits, inhaled corticosteroids have been associated with adverse local effects. These include oral candidiasis and dysphonia. However, though these risks have been reported, they have not been carefully studied. The incidence of oral candidiasis in newly treated subjects and its onset within a carefully monitored timeframe have not been adequately assessed.

A more overtly undesirable effect is dysphonia. Data on it are usually collected from spontaneous reports by patients in clinical trials. However, awareness of dysphonia requires a certain degree of subjective discomfort to initiate the report. Subjective awareness of dysphonia often varies based on an individuals voice requirements. A singer, for example, is usually acutely aware of minor voice changes in contrast to someone who does not depend on voice quality. Nonetheless, voice abnormalities can probably occur with similar frequency in patients who are concerned or not concerned with their voice due to inhaled corticosteroids. New subjective scales for reporting on an individual’s voice have recently been validated and published in other areas. These scales have not been validated in patients with asthma or in subjects using inhaled corticosteroids. New technologies for objective voice assessment have also been developed and these permit greater ability to quantify voice changes. These advances permit better measures of the potential adverse effects of inhaled corticosteroids on voice both with regard to onset of abnormalities and with regard to magnitude of effects.

This pilot study is an initial probe into clarifying the potential of the inhaled corticosteroid, fluticasone propionate delivered in the Advair DISKUS device to produce oral candidiasis and voice changes, and to determine the best measurement to quantitate objectively that effect.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or Female, 18-55 years of age. Females will be eligible only if they are:
1. Surgically sterilized, post-menopausal, abstinent, or practicing adequate method of birth control, and if they have a
2. Negative urine pregnancy test (females of childbearing potential)
History of mild persistent asthma for at least 6 months as defined by NIH NHLBI April 19971

At Visit 1 (Screening) treatment for the last 30 days prior to screening must be:

No inhaled corticosteroid therapy. (Previous use of leukotriene receptor antagonists, and/or cromones, in addition to bronchodilators also allowed.)

Exclusion Criteria:

Female subjects who are pregnant or trying to become pregnant
Breast feeding
Current patient reported hoarseness or sore throat
Presence of oropharyngeal thrush (as determined by investigator examination without culture results)
Unresolved fungal, viral or bacterial infection elsewhere in the body
Viral or bacterial respiratory tract infection within the last 14 days
History of persistent gastro-esophageal reflux refractory to conventional treatment within the last 30 days
Has smoked within the previous 6 months or has greater than a lifetime 10 pack-year smoking history or regular exposure to environmental tobacco smoke
History of inflammatory arthritis requiring immunosuppressive or corticosteroid therapy
History of glaucoma, cataracts (lens opacities), retinal disease, or blindness
Any serious concomitant disease such as cancer or serious renal, hepatic, cardiac, immunodeficiency, neurological, psychiatric, or other disease
Any medical condition that, in the judgment of the investigator, might interfere with the study, require treatment or make implementation of the protocol or interpretation of the study results difficult
Active or quiescent tuberculosis infections of the respiratory tract
History of chronic bronchitis, COPD or emphysema
History of alcohol abuse (more than 2 drinks/day on average) or drug abuse within the past 2 years
History within the last 2 years of moderate asthma requiring prednisone on more than two occasions per year
Treatment with any investigational drug within the past 30 days
More than 1 short (less than 2 weeks) course of systemic corticosteroids in the previous year prior to screening (Visit 1) or have had systemic corticosteroids in the past pervious 2 months prior to Visit 1.
Subjects can be on maintenance immunotherapy but cannot have begun an immunotherapy regimen or have had a change in their immunotherapy regimen within 30 days prior to screening (Visit 1).
Subjects may be on intranasal steroid if it has been maintained for 4 weeks prior to screen and a constant stable dose is maintained for the duration of the trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00235053

Locations

United States, California
Allergy & Asthma Medical Group & Research Center
San Diego, California, United States, 92123

Sponsors and Collaborators

Allergy & Asthma Medical Group & Research Center

Investigators

Principal Investigator:

Eli O Meltzer, MD

Allergy & Asthma Medical Group & Research Center

More Information

No publications provided

Study ID Numbers:	NONE0-L00081
Study First Received:	October 6, 2005
Last Updated:	January 30, 2006
ClinicalTrials.gov Identifier:	NCT00235053 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Allergy & Asthma Medical Group & Research Center:

asthma
candidiasis, oral
voice disorders

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Mouth Diseases
Respiratory System Agents
Neurotransmitter Agents
Candidiasis, Oral
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Bronchial Diseases
Candidiasis
Physiological Effects of Drugs
Albuterol
Reproductive Control Agents
Adrenergic Agonists
Mycoses
Signs and Symptoms

Hypersensitivity
Lung Diseases, Obstructive
Pathologic Processes
Tocolytic Agents
Respiratory Tract Diseases
Therapeutic Uses
Fluticasone
Laryngeal Diseases
Dermatologic Agents
Disease
Otorhinolaryngologic Diseases
Salmeterol
Adrenergic beta-Agonists
Immune System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on February 08, 2010