Interaction in Chronic Obstructive Pulmonary Disease Experiment (ICE)

A Hazardous Combination of Cigarette Smoking and Bronchodilation in Chronic Obstructive Pulmonary Disease

The final purpose of this study is to determine whether bronchodilation and cigarette smoking in Chronic Obstructive Pulmonary Disease (COPD) patients interact, resulting in an increase of cardiovascular disease. The aim of this part of the study is to demonstrate the basic mechanism: Does increased respiratory function after administration of a bronchodilator in patients with COPD lead to elevated pulmonary retention of the harmful compounds in inhaled cigarette smoke and to short-term biological effects associated with cardiovascular disease?

Study Overview

• Status: Completed
• Conditions: Smoking; Cardiovascular Disease; Chronic Obstructive Pulmonary Disease; Bronchodilation
• Intervention / Treatment: Drug: Tiotropium (Spiriva) + Salbutamol (Ventolin); Drug: placebo

Detailed Description

COPD currently is one of the most frequent diseases. In more than 80% of COPD patients, the disease is caused by smoking. About half of the COPD patients are active smokers, although smoking is also the most important prognostic factor. Also, smoking is an important cause as well as an important prognostic factor in cardiovascular disease. The corner stone of medical treatment in COPD is bronchodilation; more than half of the patients use a long-acting bronchodilator. An increase of the pathogenic effect of smoking by an increased lung function after bronchodilation is likely though, since more pathogenic particles would penetrate the lung. We hypothesize that bronchodilators increase cardiovascular disease in COPD patients who smoke.

In order to demonstrate the basic mechanism of our hypothesis, COPD patients receive a bronchodilator at one time and a placebo at another time, preceded and followed by cigarette smoking during one hour as by a strict time schedule. Smoke retention, lung function and blood biomarkers are repeatedly measured.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groesbeek, Netherlands
    • University Center for Chronic Diseases Dekkerswald
  • Nijmegen, Netherlands
    • Primary care, general practitioners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• COPD Gold stage II-III (FEV1/FVC<0,70 and FEV1 30-80% of predicted value).
• Current cigarette smoking (at the time of performing the study).
• Willing to provide written informed consent.
• Refrain from smoking and bronchodilators > 8 hours (depends on treatment) before the test.
• Registered in one of the recruitment institutes.

Exclusion Criteria:

• COPD gold stage I or IV.
• Asthmatic component: History of asthma, present asthma by complaints, eosinophilia or reversibility ≥ 10% of predicted.
• Unable to communicate.
• Physically unable to perform any of the tests.
• Non-COPD respiratory disorders.
• Previous lung-volume reduction surgery and/or lung transplantation.
• Evidence of alcohol, drug or solvent abuse.
• Known α-1 antitrypsin deficiency.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: beta 2 agonist + anticholinergic aerosol	Drug: Tiotropium (Spiriva) + Salbutamol (Ventolin); 1 time inhalation of 5 mcg of Tiotropium bromide by Respimat and 400 mcg of Salbutamol by Volume Spacer. cigarette smoking; Other Names: Spiriva Respimat; Ventolin Aerosol
Placebo Comparator: placebo inhalation	Drug: placebo; 1 time inhalation of placebo with the amount of puffs similar to the active comparator. cigarette smoking; Other Names: Ventolin placebo and Spiriva placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
cigarette smoke retention	retention measurement is during smoking. smoking is 1 cigarette before and 1 cigarette 45 minutes after medication inhalation for each arm. 1 week between arms

Secondary Outcome Measures

Outcome Measure	Time Frame
(hs)CRP	3 times within 2 hours for each arm
fibrinogen	3 times within 2 hours for each arm
respiratory function	at baseline and repeatedly around medication inhalation for 1.5 hours
smoking pattern: smoke inhalation and smoke exhalation time and volume	during smoking cigarettes: twice for each arm.

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Tjard RJ Schermer, PhD, Radboud University Nijmegen Medical Center

Publications and helpful links

General Publications

• van Dijk WD, Heijdra Y, Lenders JW, Klerx W, Akkermans R, van der Pouw A, van Weel C, Scheepers PT, Schermer TR. Cigarette smoke retention and bronchodilation in patients with COPD. A controlled randomized trial. Respir Med. 2013 Jan;107(1):112-9. doi: 10.1016/j.rmed.2012.09.019. Epub 2012 Oct 12.
• van Dijk WD, Scheepers PT, Cremers R, Lenders JW, Klerx W, van Weel C, Schermer TR, Heijdra Y. A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial. Trials. 2011 Feb 10;12:37. doi: 10.1186/1745-6215-12-37.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 21, 2009
• First Submitted That Met QC Criteria: September 21, 2009
• First Posted (Estimate): September 22, 2009

Study Record Updates

• Last Update Posted (Estimate): July 6, 2011
• Last Update Submitted That Met QC Criteria: July 4, 2011
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: COPD; intervention study; interaction
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Cardiovascular Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Tiotropium Bromide
• Other Study ID Numbers: RvB08.066.51196/GE