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Glittre ADL-test: Responsiveness to Acute Bronchodilation in Chronic Obstructive Pulmonary Disease (COPD)

Not Applicable
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Drug: Bronchodilators
Drug: Placebos
Registration Number
NCT03071731
Lead Sponsor
Laval University
Brief Summary

This project is aimed to assess the responsiveness of the Glittre ADL-test and the 1-Minute Sit-to-Stand test (1-Minute STST) to acute bronchodilation in patients with COPD. We also aim to investigate the physiological and perceptual response to bronchodilation of the Glittre ADL-test and the 1-minute STST. The specific objectives are 1)To measure the changes in time for completion of the Glittre ADL-test and the number of standing up during the 1-minute STST induced by a single dose of nebulized ipratropium bromide/salbutamol sulfate against those induced by a placebo in patients with moderate to severe COPD and 2)To compare in patients with moderate to severe COPD the CR (minute ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2) and heart rate) and symptomatic (dyspnea and leg fatigue perception) responses during the Glittre ADL-test and the 1-Minute STST following a single dose of ipratropium bromide/salbutamol sulfate or placebo. We suppose among others that the Glittre test completion time will be lesser, that the number of repetitions in the 1-Minute STST will be higher and symptoms intensity will be lesser among patients with COPD receiving bronchodilators.

Detailed Description

METHODOLOGY: Study design and setting: It will be a randomized double-blind trial during which 34 patients with moderate to severe COPD will complete 2 Glittre ADL-tests 15 minutes following nebulization of a placebo or of ipratropium bromide/salbutamol sulfate combination. Patients receiving bronchodilators before the beginning of the study will be asked to withdraw from their medication 8h in the case of short-acting bronchodilators and/or 72 h in the case of long-acting bronchodilators before visits. Those treated with tiotropium will have a 4-week washout period during which this therapy will be replaced by ipratropium bromide. The study will require 3 visits to the research center of Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval (IUCPQ). The 1st visit will be devoted to verify the eligibility to the study, obtain informed consent, and measure baseline characteristic including anthropometric measurements, pulmonary, and lower limb muscle function, as well maximal exercise capacity and participation in activities of daily life. In addition, participants will be familiarized with the Glittre test. During the following visits, subjects will complete two Glittre tests (1/visit) preceded by administration of nebulized placebo or ipratropium bromide/salbutamol sulfate (500 mg/2.5 mg) administrated in a randomized and double-blind fashion. Study visits will be separated by \>72 h and \<7 days. Subjects will be scheduled to attend at the same time of day throughout the study. Ethics approval will be obtained before starting the project and all subjects will provide written informed consent prior to testing. Procedure and measurements: Anthropometric measurements: Weight and height will be measured on a standing scale. Pulmonary function: Complete pulmonary function tests including spirometry, lung volumes and diffusing capacity for carbon monoxide will be obtained according to standardized technique and expressed as a percent of predicted9. In addition, during visit 2 and 3, a spirometry (FEV1 and FVC) will be obtained before and after bronchodilation to determine bronchodilator-induced change in FEV1 and baseline respiratory condition before functional tests. Muscle function: Quadriceps muscle function (force, endurance and fatigue) will be quantified during a knee extension test. The test will consist of one set of 30 repetitions at an angular velocity of 90°/s. Amplitude and angular velocity will be controlled using a dynamometric isokinetic system (Biodex, system pro 4, Biodex Medical System, Shirley, NY, USA). Maximal exercise capacity: Maximal exercise capacity will be assessed using a symptom-limited incremental cycling test. Subjects will be seating on an electrically braked ergocycle (Quinton Corival 400; A-H Robins, Seattle, WA) and connected to a portable a gas analysis system (Oxycon Mobile, Viasys Healthcare, Jaeger, Germany). After 5 minutes of rest, a progressive stepwise exercise test will be performed up to the individual maximal capacity. Each exercise step lasts 1 minute and increments of 10 watts will be applied. Minute ventilation (VE), oxygen uptake (VO2), and CO2 excretion (VCO2) respiratory exchange ratio (RER), respiratory rate (RR) inspiratory capacity (IC) and heart rate (HR) will be measured at rest and during exercise on a breath-by-breath basis. In addition, pulsed oxygen saturation (SpO2) will be measured at rest, continuously during the tests, and at end-exercise by pulse oximetry (OSM2 Hemoximeter; Radiometer,Copenhagen, Denmark). Dyspnea and leg fatigue perception will be measured by a modified Borg scale at rest, each 2 minutes and at the end of exercise. Participation in activities of daily life: Participation in activities of daily life will be measured with an accelerometer-based activity monitor (DynaPort Minimod, McRoberts BV, The Hague, The Netherlands). Patients will be instructed to wear the monitor on the waist for 7 consecutive days. They will also fill a diary of activities through the week they are wearing the physical activity monitor. Self-efficacy: Patients' perceived walking and climbing stairs confidence (on flat ground, with and without handrail) will be assessed with the 10-item self-report modified Gait Efficacy Scale. Functional tests: The Glittre ADL tests will be completed according to the original procedure described by Skumlien5. Briefly, patient carrying a weighted backpack (2.5 kg for women, 5.0 kg for men) will be instructed to stand up and walk along a flat 10-m long course. In the middle of the course, there will be a 2-step staircase (each step 17 cm high×27 cm deep) to get across. After completing the second 5 m, the subject will be facing a shelf containing 3 objects, each weighing 1 kg, positioned on the top shelf (shoulder height). Participants will then move objects, 1 by 1, to the bottom shelf (waist height) and then to the floor. Once completed, participants will then have to return the objects, always 1 by 1, to the bottom shelf and finally to the top shelf again. Participants will then walk back along the circuit, climbing and descending the stairs, until reaching the starting point (chair); sitting down and immediately beginning the next lap. Patients will be instructed to complete 5 laps on this circuit as quickly as possible. The 1-minute STST will be completed according to the procedure described by Ozalevli and al. Patients will be instructed to fully stand up from a chair, arms across the chest, sit back down and repeat as often as possible during one minute. Physiological measures as well as dyspnea and leg fatigue perception will be acquired with the same methodology used for the maximal exercise capacity. The order of functional tests will be randomized for each patient. Patients will also fill the Multidimensional Dyspnea Profile questionnaire. Global rating of change: Patients' perception of change in their performance, dyspnea and leg fatigue induced by the functional tests will be ascertain with a 7-point Likert Scale ranging from -3 (large deterioration) to +3 (large improvement) immediately after each functional test. No feedback from the evaluator will be given to patients before patients' own rating.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
34
Inclusion Criteria
  • Diagnosis of moderate to severe COPD based on the GOLD spirometric classification
  • able to provide written informed consent
  • able to follow verbal directions for testing.
Exclusion Criteria
  • diagnosed with cardiovascular, neurological or, neuromuscular conditions that could affect ability to perform the tests (e.g. stroke, knee osteoarthritis);
  • currently participating in a structured exercise or pulmonary rehabilitation program or been involved in pulmonary rehabilitation in the past 6 months;
  • experienced a COPD exacerbation in the past 6 weeks
  • receiving a daily dose > 10mg of oral Prednisone within the past 3 months
  • unable to walk 4 metres without use of a gait aid (e.g. walker, cane)
  • receiving oxygen supply

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
BronchodilatorsPlacebosNebulization of ipratropium bromide/salbutamol sulfate (500 µg/2.5 mg) before the administration of the Glittre ADL-test
PlaceboBronchodilatorsNebulization of a placebo before the administration of the Glittre ADL-test
PlaceboPlacebosNebulization of a placebo before the administration of the Glittre ADL-test
BronchodilatorsBronchodilatorsNebulization of ipratropium bromide/salbutamol sulfate (500 µg/2.5 mg) before the administration of the Glittre ADL-test
Primary Outcome Measures
NameTimeMethod
Glittre ADL-test time completionBetween 2 and 12 minutes for each test; up to three days between the two tests

Time to complete 5 laps as fast as possible

Secondary Outcome Measures
NameTimeMethod
Accelerometry-subdurationUp to three days between the two administrations

Subduration (in seconds) in the Glittre ADL-test for each component, in each lap

AccelerometryUp to three days between the two administrations

Vertical and horizontal acceleration and deceleration (m/s) in the 1-minute STST for each repetition.

Physiological variable-ventilationUp to 10 days between the cardiopulmonary maximal exercise test on the bike and the first 1-minute STST, and up to 13 days between the test on the bike and the 2nd 1-minute STST

Minute ventilation (VE; L/min) during the two 1-minute STST compared to the VE during an incremental cardiopulmonary maximal exercise test on bike.

Physiological variables-VO2 and VCO2Up to 10 days between the cardiopulmonary maximal exercise test on the bike and the first 1-minute STST, and up to 13 days between the test on the bike and the 2nd 1-minute STST

VO2 and VCO2 during the two 1-minute STST compared to those during an incremental cardiopulmonary maximal exercise test on bike.

Number of repetitions 1-Minute STSTAbout 2-3 minutes for test administration including instructions and demonstration; up to 3 days between both administration

Number of full stand-up repetitions in the 1-Minute STST in both conditions (following the administration of the placebo and the bronchodilators)

Perceptual variablesUp to three days between the two administrations

Dyspnea and fatigue in the legs at the end of the 1-minute STST

Breathing discomfortUp to three days between the two administrations

Overall subjective experience of breathing discomfort after the 1-minute STST assessed with the Multidimensional Dyspnea Profile questionnaire

Accelerometry-stepsUp to three days between the two administrations

Number of steps in the Glittre ADL-test for each walking section, in each lap

HyperinflationIn a 5-minute time frame for the IC measures at the beginning and at the end of the 1-minute STST, and up to 3 days before the 2nd assessment

Change of IC between the beginning and end of the 1-minute STST completed after the administration of the placebo compared with the change of IC between the beginning and end of the 1-minute STST after the administration of the combination of bronchodilators

Physiological variable-ratio exchange rateUp to 10 days between the cardiopulmonary maximal exercise test on the bike and the first 1-minute STST, and up to 13 days between the test on the bike and the 2nd 1-minute STST

Ratio exchange rate (RER) the two 1-minute STST compared to RER during an incremental cardiopulmonary maximal exercise test on bike.

Physiological variable-HRUp to 10 days between the cardiopulmonary maximal exercise test on the bike and the first 1-minute STST, and up to 13 days between the test on the bike and the 2nd 1-minute STST

Peak Heart rate (HR; beats/minute) during the two 1-minute STST compared to peak heart rate during an incremental cardiopulmonary maximal exercise test on bike.

Physiological variable-RRUp to 10 days between the cardiopulmonary maximal exercise test on the bike and the first 1-minute STST, and up to 13 days between the test on the bike and the 2nd 1-minute STST

Peak respiratory rate (breaths/min) during the two 1-minute STST compared to peak heart rate during an incremental cardiopulmonary maximal exercise test on bike.

Trial Locations

Locations (1)

Centre de recherche-Institut Universitaire de Cardiologie et Pneumologie de Québec

🇨🇦

Quebec City, Quebec, Canada

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