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

Early Phase 1

Completed

Conditions: Chronic Obstructive Pulmonary Disease
Chronic Bronchitis

Interventions: Drug: Tiotropium

Registration Number: NCT00870896

Lead Sponsor: ThomasTruncale

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

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 5

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tiotropium	Tiotropium	Cough reflex measured by capsaicin Inhalation Challenge will follow Dicpinigaitis performed at 1 and 3 months. Solutions prepared to make a stock solution of 0.01 Mol diluted with physiologic saline to yield 11 doubling concentrations from 0.98 to 1,000 uMol/L. Final diluted capsaicin concentrations are: 0.98, 1.95, 3.9, 7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 uMol/L. Then, place 1 ml of the first concentration into nebulizer. Subjects inhale single breath of capsaicin aerosol. Single breaths are delivered in ascending order, with normal saline randomly interspersed to increase blindness, until two or more coughs (C2) and five or more coughs (C5) are reached. The different concentrations are delivered at 2 minute intervals.

Primary Outcome Measures

Name	Time	Method
Number of Coughs Following Capsaicin Inhalation Challenge at Baseline and Following 30 Days of Treatment With Spiriva (Baseline and 30 Days)	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

Secondary Outcome Measures

Name	Time	Method
Change in FEV1 (in Liters)	30 days	Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva
Change in FEV1/FVC Ratio	30 days	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

Trial Locations

Locations (2): University of South Florida (COPH)
🇺🇸
Tampa, Florida, United States
James A Haley Veterans' Hospital
🇺🇸
Tampa, Florida, United States