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Effects of Dual Bronchodilator Treatment on Cardiopulmonary Interactions in COPD

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ClinicalTrials.gov Identifier: NCT03425617
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : February 8, 2018
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Dr. J. Alberto Neder, Queen's University

Brief Summary:
The deleterious consequences of lung hyperinflation seem not to be restricted to the respiratory system in patients with chronic obstructive pulmonary disease (COPD). Cardiac function, in particular, is strongly influenced by changes in lung volumes and intra-thoracic pressures. In this context, strategies to reduce lung hyperinflation and the work of breathing can positively impact upon cardiac output and blood flow redistribution to peripheral muscles in these patients. There is growing evidence that combination of bronchodilators of different classes is an efficacious and safe strategy for further improving airflow obstruction and hyperinflation in patients with more advanced COPD. Therefore, we aim to investigate that, compared with placebo, a novel LABA/LAMA fixed combination (tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® (Inspiolto®) (TIO/OLO) would decrease lung volumes at rest and during exercise, thereby improving: 1) central and peripheral hemodynamics and 2) arterial oxygenation, with positive consequences on skeletal muscle oxygenation and exercise tolerance in hyperinflated patients with moderate to very severe COPD.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Tiotropium + Olodaterol Other: PLACEBO Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Dual Bronchodilator Treatment (Tiotropium + Olodaterol Respimat) on Cardiopulmonary Interactions in Hyperinflated Patients With COPD
Actual Study Start Date : January 1, 2017
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Tiotropium + Olodaterol first
tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 3 followed by PLACEBO via Respimat® single dose in Visit 4
Drug: Tiotropium + Olodaterol
tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose
Other Name: INSPIOLTO®
Other: PLACEBO
PLACEBO via Respimat® single dose
Experimental: PLACEBO FIRST
Placebo via Respimat® single dose in Visit 3 followed bytiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 4
Drug: Tiotropium + Olodaterol
tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose
Other Name: INSPIOLTO®
Other: PLACEBO
PLACEBO via Respimat® single dose



Primary Outcome Measures :
  1. Blood Flow Index (BFI) [ Time Frame: 1 day ]
    Near infrared spectroscopy (NIRS)-derived muscle ICG difference divided by the rise time from 10 to 90% of peak.


Secondary Outcome Measures :
  1. Cardiac output [ Time Frame: 1 day ]
    Cardiac output measured by thoracic cardioimpedance

  2. Muscle oxygenation [ Time Frame: 1 day ]
    Deoxy-hemoglobin (HHb) has been selected as a proxy for muscle fractional O2 extraction and expressed relative to maximum values elicited by cuff-induced ischemia.

  3. Tlim [ Time Frame: 1 day ]
    Exercise tolerance during hugh intensity constant load exercise test (75% of peak workload)

  4. Exercise dyspnea [ Time Frame: 1 day ]
    Borg score rated during isotime and peak exercise

  5. Inspiratory capacity [ Time Frame: 1 day ]
    Inspiratory capacity, inspiratory reserve volume measured at rest, isotime and peak exercise

  6. Inspiratory reserve volume [ Time Frame: 1 day ]
    Inspiratory reserve volume measured at rest, isotime and peak exercise



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Ages Eligible for Study:   50 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥50 years;
  2. Male or female gender;
  3. Long-term history of active smoking;
  4. Signs and symptoms of COPD with adequate treatment according to the GOLD recommendations for at least 3 months (1);
  5. A modified MRC dyspnea score ≥2 or a Baseline Dyspnea Index ≤8;
  6. Resting lung hyperinflation as demonstrated by inspiratory capacity <80% predicted or functional residual capacity >120% predicted at Visit 1;
  7. Objective evidence of dynamic hyperinflation (a decrease in inspiratory capacity from rest >200 mL)(24,25) and peak exercise dyspnea (breathing discomfort) ≥ leg discomfort scores during the incremental cardiopulmonary exercise test at Visit 1;
  8. A positive "volume" response (≥200 mL increase in inspiratory capacity) to a bronchodilator (400μg salbutamol) at Visit 1
  9. Ability to perform all study procedures and provide/sign informed consent.

Exclusion Criteria:

  1. Asthma or other concomitant pulmonary disease;
  2. Use of oral steroids in the preceding month;
  3. Orthopedic/rheumatological limitation precluded cycling;
  4. Type I or non-controlled type II diabetes mellitus or other endocrine diseases;
  5. Unstable angina, life-threatening cardiac arrhythmias, use of an implantable defibrillator;
  6. Myocardial infarction within the previous 6 months;
  7. History of long QT syndrome (or prolonged corrected QT interval (>450 ms during screening);
  8. Clinically significant ECG abnormality;
  9. History of exercise-induced syncope;
  10. Any contraindication for exercise testing;
  11. Inability to understand and cooperate with the procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425617


Contacts
Contact: Filipa Saramago, RA 16135496666 ext 3197 fs43@queensu.ca
Contact: Danilo Berton, MD 6135396021 ext 3199 db177@queensu.ca

Locations
Canada, Ontario
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, k7l2v7
Contact: J Alberto Neder, MD    16135496666 ext 3198    nederalb@gmail.com   
Contact: Filipa Saramago    16135496666 ext 3197    fs43@queensu.ca   
Sponsors and Collaborators
Queen's University
Boehringer Ingelheim
Investigators
Principal Investigator: J Alberto Neder, Prof Queen'sUniversity/Kingston General Hospital

Responsible Party: Dr. J. Alberto Neder, Clinical professor, Queen's University
ClinicalTrials.gov Identifier: NCT03425617     History of Changes
Other Study ID Numbers: 6018318
First Posted: February 7, 2018    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Tiotropium Bromide
Bronchodilator Agents
Olodaterol
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents