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

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
ThomasTruncale, University of South Florida
ClinicalTrials.gov Identifier:
NCT00870896
First received: March 25, 2009
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Chronic Bronchitis
Drug: Tiotropium
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Tiotropium on the Cough Reflex in Patients With COPD

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • Number of Coughs Following Capsaicin Inhalation Challenge at Baseline and Following 30 Days of Treatment With Spiriva (Baseline and 30 Days) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva

  • Change in FEV1/FVC Ratio [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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


Enrollment: 5
Study Start Date: February 2008
Study Completion Date: June 2012
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.
Other Name: Spiriva

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

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00870896

Locations
United States, Florida
James A Haley Veterans' Hospital
Tampa, Florida, United States, 33612
University of South Florida (COPH)
Tampa, Florida, United States, 33612
Sponsors and Collaborators
ThomasTruncale
Boehringer Ingelheim
Investigators
Principal Investigator: Thoms Truncale, DO,MPH University of South Florida
  More Information

Publications:
CIBA Guest symposium Report. Terminology, definitions and classifications of chronic pulmonary emphysema and related conditions. Thorax 1959; 14: 286-289.
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.
American Thoracic Society: Guidelines for Methacholine and Exercise Challenge Testing AJRCCM 2000; 161(1): 309-329.

Responsible Party: ThomasTruncale, Associate porfessor, University of South Florida
ClinicalTrials.gov Identifier: NCT00870896     History of Changes
Other Study ID Numbers: P65201, 0800000250 V10
Study First Received: March 25, 2009
Results First Received: June 13, 2012
Last Updated: September 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of South Florida:
capsaicin
COPD
COPD with chronic bronchitis

Additional relevant MeSH terms:
Bronchitis
Bronchitis, Chronic
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014