Clinical trial NCT00870896: The Effects of Tiotropium on the Cough Reflex in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: The Effects of Tiotropium on the Cough Reflex in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Chronic Bronchitis
Keywords: capsaicin
COPD
COPD with chronic bronchitis
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2009-03-27
Enrollment: 5
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Does tiotropium effect the cough reflex in patients with COPD and chronic bronchitis.

Detailed description: Cough Questionnaire

This questionnaire is designed to assess the impact of cough on various aspects of your life. Read each question carefully and answer by CIRCLING the response that best applies to you. Please answer ALL questions, as honestly as you can.

1. In the last 2 weeks, have you had chest or stomach pains as a result of your cough? 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
2. In the last 2 weeks, have you been bothered by sputum (phlegm) production when you cough? 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
3. In the last 2 weeks, have you been tired because of your cough? 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
4. In the last 2 weeks, have you felt in control of your cough? 1 2 3 4 5 6 7 None of the time Hardly any time A little of the time Some time A good bit of time Most of the time All of the time
5. How often during the last 2 weeks have you felt embarrassed by your coughing? 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
6. In the last 2 weeks, my cough has made me feel anxious 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
7. In the last 2 weeks, my cough has interfered with my job, or other daily tasks 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
8. In the last 2 weeks, I felt that my cough interfered with the overall enjoyment of my life 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
9. In the last 2 weeks, exposure to paints or fumes has made me cough 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time
10. In the last 2 weeks, has your cough disturbed your sleep? 1 2 3 4 5 6 7 All of the time Most of the time A good bit of time Some time A little of the time Hardly any time None of the time

Eligibility criteria: Inclusion Criteria:

After signing the informed consent, screening testing will be done to document that a subject meets the requirements of the study. Specific inclusion criteria are:

* Subjects between the ages of 40 and 80 years of age (Dates of Birth 1925-1965)
* Current smoker (with smoking history of \> 10 pack/year) or ex-smoker (stopped within 1 year and has at least a 10 pack/year smoking history).
* Subjects will be included if they meet criteria for mild and moderate COPD as defined by the American Thoracic Society and European Respiratory Society position paper. Mild COPD will be defined as a postbronchodilator (2 puffs of albuterol) FEV1/FVC ratio of \<0.7 and a predicted FEV1 of \> 80%. Moderate COPD will be defined as a postbronchodilator FEV1/FVC ratio of \<0.7 and a predicted FEV1 50-80%. A response to bronchodilators is defined as an increase of 12% or 200cc in FEV1 from baseline after inhalation of 2 puffs of albuterol. Both subjects with and without a response to bronchodilators will be included in the study.
* All subjects will be clinically stable for 4 weeks prior to inclusion. Clinical stability is defined as having no recent COPD exacerbations within the last 4 weeks and having received no antibiotics or change in their inhaled steroid dose during that time period. If a subject is on oral steroids, they will be required to be on 10 mg or less each day or no more than 20mg every other day to be eligible. If the oral steroid dose has been titrated over the previous 4 weeks (either up or down) or if the dose is higher than what has been described previously, they will be ineligible for the study.
* All subjects will be off of tiotropium or ipratropium for 1 month prior to the start of the study.
* Chronic cough: Chronic cough will be characterized by the presence of a productive cough for 3 months in each of 2 successive years in persons in whom other causes of chronic cough have been excluded.

Exclusion Criteria:Exclusion Criteria: Subjects will not be eligible for the study if they are

* Age of \< 40 or \> 80 years.
* Refusal to volunteer for the study and not willing to sign the informed consent form.
* Respiratory disorder other than COPD including asthma, chronic bronchiectasis or pulmonary fibrosis
* Oxygen or ventilator dependent COPD.
* Received any antibiotics or had a change in their inhaled steroid dose during the last 4 weeks. If a subject is on oral steroids, they will be required to be on 10 mg or less each day or no more than 20mg every other day to be eligible. If the oral steroid dose has been titrated over the previous 4 weeks (either up or down) or if the dose is higher than what has been described previously, they will be ineligible for the study.
* History of Congestive heart failure, cardiomyopathy, valvular heart disease, angina, cardiac arrhythmia, or myocardial infarction within the last 6 months or poorly controlled hypertension.
* History of chronic hepatitis or hepatic cirrhosis.
* End-stage renal disease.
* History of neurologic or psychiatric disorder which would interfere with completion of the study.
* Physician diagnosis of Gastroesophageal reflux disease
* Physician diagnosis of allergic, non-allergic rhinitis, or sinusitis
* History of lung cancer
* History of radiation treatment to the chest or mediastinum
* Lung volume reduction surgery, segmentectomy, lobectomy or pneumonectomy
* History of a thoracotomy
* Symptomatic Benign prosthetic hypertrophy
* Symptomatic bladder outlet obstruction
* Symptomatic glaucoma
* Severe COPD defined as a postbronchodilator FEV1/FVC ratio of \< 0.7 and a predicted FEV1 of 30-50%. Very severe COPD defined as a postbronchodilator FEV1/FVC ratio of \<0.7 and a predicted FEV1 of \< 30%. (Eur Respir J 2004; 23: 932-946).
* Within the previous one month (30 days) prior to beginning the study, used or continue to use ipratropium or tiotropium
* Allergic response or history of allergy to lactose

Primary outcomes:
measure: Number of Coughs Following Capsaicin Inhalation Challenge at Baseline and Following 30 Days of Treatment With Spiriva (Baseline and 30 Days)
timeFrame: 30 days
Secondary outcomes:
measure: Change in FEV1 (in Liters)
timeFrame: 30 days
measure: Change in FEV1/FVC Ratio
timeFrame: 30 days
Other outcomes:
Locations:
city: Tampa
country: United States
facility: James A Haley Veterans' Hospital
state: Florida
city: Tampa
country: United States
facility: University of South Florida (COPH)
state: Florida
Study officials:
affiliation: University of South Florida
name: Thoms Truncale, DO,MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004 Jun;23(6):932-46. doi: 10.1183/09031936.04.00014304. No abstract available.
citation: CIBA Guest symposium Report. Terminology, definitions and classifications of chronic pulmonary emphysema and related conditions. Thorax 1959; 14: 286-289.
citation: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 2):S77-121. No abstract available.
citation: Doherty MJ, Mister R, Pearson MG, Calverley PM. Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax. 2000 Aug;55(8):643-9. doi: 10.1136/thorax.55.8.643.
citation: Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339-43. doi: 10.1136/thorax.58.4.339.
citation: Sekizawa K, Jia YX, Ebihara T, Hirose Y, Hirayama Y, Sasaki H. Role of substance P in cough. Pulm Pharmacol. 1996 Oct-Dec;9(5-6):323-8. doi: 10.1006/pulp.1996.0042.
citation: Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999 Jun;51(2):159-212. No abstract available.
citation: Midgren B, Hansson L, Karlsson JA, Simonsson BG, Persson CG. Capsaicin-induced cough in humans. Am Rev Respir Dis. 1992 Aug;146(2):347-51. doi: 10.1164/ajrccm/146.2.347.
citation: Fujimura M, Sakamoto S, Kamio Y, Matsuda T. Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. Thorax. 1992 Jun;47(6):441-5. doi: 10.1136/thx.47.6.441.
citation: Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309-29. doi: 10.1164/ajrccm.161.1.ats11-99. No abstract available.