GOLD Stage I Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Collaborators:
Boehringer Ingelheim
Pfizer
Information provided by:
Laval University
ClinicalTrials.gov Identifier:
NCT01360788
First received: May 12, 2011
Last updated: May 24, 2011
Last verified: May 2011
  Purpose

Recently integrated in clinical practice, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification states that a mild (stage I) chronic obstructive pulmonary disease (COPD) is present, in a smoker, when the postbronchodilator forced expired volume in 1 second (FEV1) to forced vital capacity (FVC) ratio is < 0.7. A major change that was introduced by the GOLD classification system was that COPD could be diagnosed despite an FEV1 that is within normal predicted values (above 80% predicted). Because it suggests diagnosing and detecting COPD earlier than done until very recently in medical practice, the GOLD standards bring in a new reality to clinicians. In fact, this novel COPD classification comes with new research challenges because the functional impacts and systemic consequences related to COPD are mostly documented in patients with moderate to severe stages with little information specifically in GOLD stage I COPD. This information is important if the investigators are to convince physicians that GOLD stage I COPD needs to be diagnosed and eventually treated.

The investigators aimed to characterize GOLD stage I COPD patients according to activity-related dyspnea. More specifically, our objectives were to compare:

i) baseline pulmonary function ii) exercise capacity iii) quadriceps muscle function iv) levels of physical activity in daily life

between symptomatic (Sx) GOLD stage I COPD patients, asymptomatic (ASx) GOLD stage I COPD patients and healthy control subjects (CTRL). The investigators reasoned that exercise tolerance and physical activity levels would be decreased in Sx GOLD stage I COPD patients as it would be similar between ASx GOLD stage I COPD patients and CTRL.


Condition Intervention
Mild Chronic Obstructive Pulmonary Disease
Respiratory Symptoms
Physical Activity
Drug: Combination ipratropium/salbutamol or placebo (nebulization)

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: GOLD Stage I COPD: Is it Really a Disease ? Exercise Tolerance, Muscle Function and Response to Bronchodilation in GOLD Stage I COPD Patients

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Maximal oxygen consumption [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Exercise capacity was directly assessed following an incremental progressive shuttle test. The exercise capacity was defined as the maximal oxygen consumption (VO2 peak, ml/kg/min) by direct measurements of gas exchanges.


Secondary Outcome Measures:
  • Quadriceps muscle force [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    Quadriceps muscle strength was measured with magnetic stimulation of the femoral nerve.

    Mid-thigh cross-sectional area (MTCSA) was obtained following a computed-tomography scan.

    Quadriceps muscle biopsy was performed to measure muscle metabolism.


  • Levels of physical activity in daily life [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    A portable armband was worn by the participants on a 7-days basis to monitor physical activities in daily life.

  • Oxydative stress [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Oxydative stress will be quantified in the blood and in the muscle samples obtained during the muscular biopsy.

  • Pulmonary function [ Time Frame: At baseline and before and 60-min after the nebulization of either placebo or bronchodilator ] [ Designated as safety issue: No ]
    Pulmonary function will be measured by spirometry and plethysmography in the initial visit. In the subsequent visits, pulmonary function will be measured by spirometry before and 60-min after the nebulization of either placebo or bronchodilator. A computed-tomography scan of the lungs was also assessed

  • Time to exhaustion during a constant intensity exercise test [ Time Frame: Before and 90-min after bronchodilation or placebo ] [ Designated as safety issue: No ]
    Time to exhaustion was also defined as exercise tolerance and was assessed during a endurance shuttle walking test 90-min following the nebulization of whether Combivent or Placebo in a double-blind crossover design. It was defined as the time in seconds for which a subject could maintain an intensity of 85% of the maximal oxygen consumption during walking or running.

  • Systemic inflammation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Systemic inflammation will be studied from blood samples obtained in every participants.

  • Quadriceps muscle endurance [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Quadriceps muscle endurance was defined as the time to exhaustion following a constant quadriceps force corresponding to 50 % of the maximal voluntary contraction.


Biospecimen Retention:   Samples Without DNA

Muscle biopsies Venous blood samples


Enrollment: 53
Study Start Date: February 2009
Study Completion Date: February 2011
Groups/Cohorts Assigned Interventions
Healthy control subjects
Subjects with a significant smoking history (more than 10 pack-years) and a normal lung function.
Asymptomatic GOLD stage I COPD patients
GOLD stage I COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] > 80% predicted and FEV1/ forced vital capacity [FVC] < 0.7 and a smoking history > 10 pack-years) were recruited. A Medical Research Council (MRC) dyspnea score ≥ 2 was used to define the presence of symptoms (dyspnea). Concretely, this group did not present any respiratory symptoms, with a MRC dyspnea score of 1/5.
Drug: Combination ipratropium/salbutamol or placebo (nebulization)
The COPD patients were randomly assigned a combination of ipratropium/salbutamol or a placebo in a double-blind crossover design. The bronchodilation produced by the medication was given in order to evaluate if bronchodilation was effective in increasing exercise tolerance during an endurance shuttle walking test in patients with GOLD stage I COPD.
Other Name: Combivent or placebo (nebulization)
Symptomatic GOLD stage I COPD patients
GOLD stage I COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] > 80% predicted and FEV1/ forced vital capacity [FVC] < 0.7 and a smoking history > 10 pack-years) were recruited. A Medical Research Council (MRC) dyspnea score ≥ 2 was used to define the presence of symptoms (dyspnea) in this group.
Drug: Combination ipratropium/salbutamol or placebo (nebulization)
The COPD patients were randomly assigned a combination of ipratropium/salbutamol or a placebo in a double-blind crossover design. The bronchodilation produced by the medication was given in order to evaluate if bronchodilation was effective in increasing exercise tolerance during an endurance shuttle walking test in patients with GOLD stage I COPD.
Other Name: Combivent or placebo (nebulization)

Detailed Description:

The study will be conducted among three subgroups: symptomatic GOLD stage I patients with COPD, asymptomatic patients GOLD stage I COPD and healthy control subjects with normal lung function. Subjects will be paired for age, sex and smoking history. The project will require three visits. In the initial visit, assessment of the pulmonary function with respiratory symptoms quantification will allow to classify subjects in the proper subgroup. The Medical Research Council (MRC) dyspnea scale will serve as the reference outcome to determine whether COPD patients are symptomatic or not. Patients with an MRC dyspnea score < 2 will be considered asymptomatic. A second questionnaire (ATS-DLD-78) will serve to document cough, expectorations, wheezing and smoking history in every subjects. Body composition will be measured by bioimpedance and by waist circumference after a blood sample taken in the morning, in a fasting state. A six-minute walk test (6MWT) will be performed by all subjects. After a one-hour resting period, a maximal incremental shuttle walking test will be realized in the same visit to quantify maximal exercise capacity. Measures of force and endurance of the quadriceps will be taken by magnetic stimulation of the femoral nerve before the maximal walking test. Finally, subjects will receive a portable device to monitor physical activity for a period of 7 days.

In the 2nd and 3rd visits, subjects will realize an endurance walking test at 85 % of their predetermined maximal capacity. Before each endurance test, a bronchodilator or a placebo will be administered following a randomized double-blind design. Measures of force and endurance of the quadriceps will be taken by magnetic stimulation of the femoral nerve before and 10-min after endurance exercise tests. A needle biopsy of the vastus lateralis will be performed at the end of the third visit.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Participants were recruted after a participation to a research protocol on i) prevalence of COPD in Canada and ii) early detection of lung cancer. Finally, some participants were recruited following medical consultation with a pneumologist.

Criteria

Inclusion Criteria:

  • Smoking history (≥ 10 pack/year)

Exclusion Criteria:

  • Anticoagulation or coagulation defect
  • Hypoxemia or exercise-induced desaturation (SpO2 < 85%)
  • Antibiotic or oral corticosteroid therapy (end of treatment < 1 month prior to study)
  • Anti-inflammatory treatment, exacerbation (< 3 months)
  • Myopathy
  • Neuromuscular or locomotor diseases
  • Recent cancer
  • Unstable cardiac condition
  • Asthma
  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: NCT01360788

Locations
Canada, Quebec
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
Québec, Quebec, Canada, G1V 4G5
Sponsors and Collaborators
Laval University
Boehringer Ingelheim
Pfizer
Investigators
Principal Investigator: François Maltais, MD Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
  More Information

No publications provided

Responsible Party: Dr François Maltais, Institut Universitaire de cardiologie et de pneumologie de Québec
ClinicalTrials.gov Identifier: NCT01360788     History of Changes
Other Study ID Numbers: GOLD-20378
Study First Received: May 12, 2011
Last Updated: May 24, 2011
Health Authority: Canada: Ethics Review Committee

Keywords provided by Laval University:
chronic obstructive pulmonary disease
lung function
symptoms
activity-related dyspnea
quadriceps muscle function
exercise capacity
physical activity in daily life
muscle biopsy
systemic inflammation
GOLD stage I
pulmonary function

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

ClinicalTrials.gov processed this record on October 23, 2014