The Effects of Tiotropium on the Cough Reflex in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

The Effects of Tiotropium on the Cough Reflex in Patients With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00870896
• Other study ID #: P65201
• Secondary ID: 0800000250 V10
• Status: Completed
• Phase: Phase 0
• First received: March 25, 2009
• Last updated: September 29, 2014
• Start date: February 2008
• Est. completion date: June 2012

Study information

• Verified date: September 2014
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: June 2012
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium
Each subject will then receive Spiriva 18 ug/day for a total of 4 weeks. Each subject will be instructed by the PI on the proper use of the Spiriva inhaler and demonstrate the ability to properly perform the inhalation technique prior to leaving the laboratory. The patient will receive their first dose in the laboratory under the direct supervision of one of the investigators. In addition, subjects will be requested to take their Spiriva inhalation treatment the same time each day.

Locations

Country	Name	City	State
United States	James A Haley Veterans' Hospital	Tampa	Florida
United States	University of South Florida (COPH)	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
ThomasTruncale	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View 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. Erratum in: Eur Respir J. 2006 Jan;27(1):242. — View Citation

Celli BR, Snider GL, Heffner J, Tiep B, et al. Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease. AJRCCM 1995; 152(5)(Pt 2): S78-S83.

CIBA Guest symposium Report. Terminology, definitions and classifications of chronic pulmonary emphysema and related conditions. Thorax 1959; 14: 286-289.

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999 Jun;51(2):159-212. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Coughs Following Capsaicin Inhalation Challenge at Baseline and Following 30 Days of Treatment With Spiriva (Baseline and 30 Days)	We measured the change in the number of coughs following capsaicin inhalation challenge from baseline followed by 30 days of treatment with spiriva	30 days	No
Secondary	Change in FEV1 (in Liters)	Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva	30 days	No
Secondary	Change in FEV1/FVC Ratio	We measured the change in FEV1/FVC ratio at baseline and following 30 days of treatment with Spiriva.Change in ratio reflects the percentage value (ratio) at 30 days minus the percentage value (ratio) at baseline x 100	30 days	No