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

NCT00870896 | Completed Early Phase 1 Results DMC

• 2 other identifiers: P652010800000250 V10
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease; Chronic Bronchitis

Keywords

capsaicin; COPD; COPD with chronic bronchitis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change in FEV1 (in Liters)

  30 days

• Change in FEV1/FVC Ratio

  30 days

Study Arms (1)

Tiotropium

EXPERIMENTAL

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

Interventions

Tiotropium DRUG

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.

Also known as: Spiriva

Tiotropium

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ThomasTruncale: lead
• Boehringer Ingelheim: collaborator

Study Sites (2)

James A Haley Veterans' Hospital

Tampa, Florida, 33612, United States

Location

University of South Florida (COPH)

Tampa, Florida, 33612, United States

Location

Related Publications (10)

• 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.

  PMID: 15219010 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 7582322 BACKGROUND

• 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.

  PMID: 10899239 BACKGROUND

• 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.

  PMID: 12668799 BACKGROUND

• 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.

  PMID: 9232670 BACKGROUND

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

  PMID: 10353985 BACKGROUND

• 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.

  PMID: 1489123 BACKGROUND

• 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.

  PMID: 1386691 BACKGROUND

• 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.

  PMID: 10619836 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Thomas Truncale
• Organization: University of South Florida

ttruncal@health.usf.edu

813 974 8952

Study Officials

• Thoms Truncale, DO,MPH

  University of South Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate porfessor

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 27, 2009
• Study Start: February 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: June 1, 2012
• Last Updated: October 1, 2014
• Results First Posted: September 15, 2014

Record last verified: 2014-09

Locations

US (2)