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

Primary Purpose

Chronic Obstructive Pulmonary Disease, Chronic Bronchitis

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tiotropium

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring capsaicin, COPD, COPD with chronic bronchitis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

James A Haley Veterans' Hospital
University of South Florida (COPH)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tiotropium

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in FEV1 (in Liters)

Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva

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

Full Information

NCT ID

NCT00870896

First Posted

March 25, 2009

Last Updated

September 29, 2014

Sponsor

ThomasTruncale

Collaborators

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00870896

Brief Title

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

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Completed

Study Start Date

February 2008 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

ThomasTruncale

Collaborators

Boehringer Ingelheim

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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. 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 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 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 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 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 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 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 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 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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease, Chronic Bronchitis

Keywords

capsaicin, COPD, COPD with chronic bronchitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tiotropium

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tiotropium

Other Intervention Name(s)

Spiriva

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

We measured the change in the number of coughs following capsaicin inhalation challenge from baseline followed by 30 days of treatment with spiriva

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Change in FEV1 (in Liters)

Description

Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva

Time Frame

30 days

Title

Change in FEV1/FVC Ratio

Description

Time Frame

30 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thoms Truncale, DO,MPH

Organizational Affiliation

University of South Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

James A Haley Veterans' Hospital

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

University of South Florida (COPH)

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15219010

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. Erratum In: Eur Respir J. 2006 Jan;27(1):242.

Results Reference

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

Results Reference

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PubMed Identifier

7582322

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.

Results Reference

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PubMed Identifier

10899239

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.

Results Reference

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PubMed Identifier

12668799

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.

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PubMed Identifier

9232670

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.

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PubMed Identifier

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Citation

Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999 Jun;51(2):159-212. No abstract available.

Results Reference

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PubMed Identifier

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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.

Results Reference

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PubMed Identifier

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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.

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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.

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

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