Trial record 25 of 71 for:    inhaler | Recruiting, Not yet recruiting, Available Studies | "Lung Diseases"

Chronic Beta-blockade and Cardiopulmonary Exercise in COPD (CPET1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02380053
Recruitment Status : Recruiting
First Posted : March 5, 2015
Last Update Posted : November 6, 2017
Information provided by (Responsible Party):
William J Anderson, University of Dundee

Brief Summary:

What are the differential effects of beta-blockers on lung and heart function during exercise in chronic obstructive pulmonary disease (COPD)? COPD is a major cause of illness and death. Not only do these individuals suffer from lung disease, but COPD often leads to other illnesses, particularly heart disease. Beta-blockers very successfully treat heart disease. It is therefore logical that one would want to use this treatment in COPD patients with heart disease too. However, there has always been concern that beta-blockers could cause significant problems in COPD by worsening lung function, as these can have the opposite effect to inhalers used to treat COPD that open up airways. Pointedly, there is increasing evidence that despite this problem, COPD patients who have been prescribed beta-blockers have been shown to gain benefit particularly in terms of preventing death.

In this study, the investigators therefore want to examine which beta-blocker might be the safest for COPD patients, as each work slightly differently. Some beta-blockers may have a more beneficial effect on airways than others, whilst still benefitting the heart. The investigators will study two different beta-blockers; one that potentially narrows airways and one that potentially opens airways. The investigators will be using cardiopulmonary exercise testing (an exercise bike that measures both heart and lung function during exercise) to look for differences between both beta-blockers primarily in terms of lung function but also with information about the heart. The investigators will recruit people with moderate to severe COPD who are able to complete a cycle exercise test through their respiratory research department. The study will last for 10-12 weeks with 5 main visits to the department for serial exercise tests, breathing tests, simple heart function tests and simple blood tests that will tell the investigators what other effects these beta-blockers are having on the heart and lungs.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Bisoprolol Drug: Celiprolol Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proof of Concept Study to Assess the Differential Effects of Chronic Beta-blockade (Celiprolol Versus Bisoprolol) on Cardiopulmonary Outcomes at Rest and During Exercise in Chronic Obstructive Pulmonary Disease
Study Start Date : June 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Bisoprolol
2.5mg once daily for 2 weeks then 5mg once daily for 2 weeks.
Drug: Bisoprolol
2 weeks of Bisoprolol 2.5mg daily then 2 weeks Bisoprolol 5mg daily
Experimental: Celiprolol
200mg once daily for 2 weeks then 400mg once daily for 2 weeks.
Drug: Celiprolol
2 weeks of Celiprolol 200mg daily then 2 weeks Celiprolol 400mg daily

Primary Outcome Measures :
  1. Change in Inspiratory Capacity (IC) from rest to isotime peak. [ Time Frame: Baseline to 4 weeks ]
    The primary outcome for this study will be the difference from baseline in the change in Inspiratory Capacity (IC) from rest to isotime peak (i.e. same time point during endurance exercise test) between beta-blocker treatments at 4 weeks. This will evaluate any differences in dynamic hyperinflation during exercise between treatments.

Secondary Outcome Measures :
  1. Exercise outcome: Oxygen uptake at peak exercise (VO2peak) [ Time Frame: Baseline to 4 weeks. ]
  2. Exercise outcome: Anaerobic threshold (AT) [ Time Frame: Baseline to 4 weeks. ]
  3. Exercise outcome: Heart rate [ Time Frame: Baseline to 4 weeks. ]
  4. Exercise outcome: Heart rate reserve (HRR) [ Time Frame: Baseline to 4 weeks. ]
  5. Exercise outcome: Heart rate recovery (HRrec) [ Time Frame: Baseline to 4 weeks. ]
  6. Exercise outcome: Respiratory rate [ Time Frame: Baseline to 4 weeks. ]
  7. Exercise outcome: Breathing reserve [ Time Frame: Baseline to 4 weeks. ]
  8. Exercise outcome: Ventilatory equivalent for oxygen at anaerobic threshold [ Time Frame: Baseline to 4 weeks. ]
    Measure of ventilatory efficiency

  9. Exercise outcome: Ventilatory equivalent for carbon dioxide at anaerobic threshold [ Time Frame: Baseline to 4 weeks. ]
    Measure of ventilatory efficiency

  10. Exercise outcome: Pulse oximetry at peak exercise [ Time Frame: Baseline to 4 weeks. ]
  11. Exercise outcome: Oxygen pulse (O2P) [ Time Frame: Baseline to 4 weeks. ]
    Surrogate for stroke volume

  12. Exercise outcome: Total exercise time [ Time Frame: Baseline to 4 weeks. ]
  13. Non-invasive cardiac output measure: Stroke volume [ Time Frame: Baseline to 4 weeks ]
  14. Non-invasive cardiac output measure: Cardiac output [ Time Frame: Baseline to 4 weeks ]
  15. Non-invasive cardiac output measure: Cardiac Index [ Time Frame: Baseline to 4 weeks ]
  16. Spirometry: Forced expiratory volume in 1s (FEV1) [ Time Frame: Baseline to 4 weeks ]
    Spirometry, Impulse oscillometry, whole body plethysmography

  17. Spirometry: Forced Vital Capacity (FVC) [ Time Frame: Baseline to 4 weeks ]
  18. Spirometry: Forced expiratory flow between 25-75% of FVC [ Time Frame: Baseline to 4 weeks ]
  19. Spirometry: FEV1/FVC ratio [ Time Frame: Baseline to 4 weeks ]
  20. Impulse oscillometry: Resistance at 5 Hertz (R5) [ Time Frame: Baseline to 4 weeks ]
    Measure of total airway resistance

  21. Impulse oscillometry: Resistance at 20 Hertz (R20) [ Time Frame: Baseline to 4 weeks ]
    Measure of large airway resistance

  22. Impulse oscillometry: Reactance at 5 Hertz (X5) [ Time Frame: Baseline to 4 weeks ]
    Measure of airway compliance

  23. Impulse oscillometry: Area under the curve [ Time Frame: Baseline to 4 weeks ]
    Measure of small airways resistance

  24. Impulse oscillometry: Frequency of resonance [ Time Frame: Baseline to 4 weeks ]
    Measure of small airways resistance

  25. Whole body plethysmography: Total lung capacity [ Time Frame: Baseline to 4 weeks ]
  26. Whole body plethysmography: Residual volume [ Time Frame: Baseline to 4 weeks ]
    Measure of air trapping in the lungs

  27. Supine blood pressure [ Time Frame: Baseline to 4 weeks ]
  28. Erect blood pressure [ Time Frame: Baseline to 4 weeks ]
  29. Change in blood B-natriuretic peptide levels [ Time Frame: Baseline to 4 weeks ]
  30. Change in blood Galectin levels [ Time Frame: Baseline to 4 weeks ]
  31. Change in blood Cholesterol/HDL levels [ Time Frame: Baseline to 4 weeks ]
  32. Change in blood creatine kinase levels [ Time Frame: Baseline to 4 weeks ]
  33. Change in blood potassium levels [ Time Frame: Baseline to 4 weeks ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female volunteers aged 40-80 years
  • Stable moderate to severe COPD (Global initiative on Obstructive Lung Disease [GOLD] stage 2/3)
  • Post-bronchodilator FEV1 30-80% predicted
  • FEV1/FVC ratio <70%
  • Stable defined as no exacerbation in previous 1 month
  • Smoking history ≥10 pack-years
  • Oxygen saturations ≥92% on room air at rest
  • Electrocardiogram demonstrating sinus rhythm.

Exclusion Criteria:

  • Use of domiciliary oxygen
  • History of other primary obstructive lung disease including asthma or bronchiectasis
  • Hospitalisation with exacerbation of COPD within past 3 months
  • History of unstable angina, uncontrolled hypertension or heart failure (New York Heart Association class 3-4)
  • Overt clinical signs of right heart failure
  • Average resting systolic BP<110mmHg or average resting HR<55bpm
  • Pregnancy or lactation
  • Known or suspected sensitivity to/intolerance of investigational medicinal product
  • Inability to comply with compulsory aspects of protocol
  • Any degree (first, second or third) of heart block
  • Sino-atrial block
  • Sick sinus syndrome
  • Severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome
  • Untreated phaeochromocytoma
  • Severe renal impairment (eGFR<15ml/min)
  • Concomitant prescription of beta-blockers, rate-limiting calcium channel blockers, digoxin, amiodarone
  • Any clinically significant medical condition that may endanger the health or safety of the participant, or jeopardise the protocol
  • Participation in another trial within the previous 30 days

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 identifier (NCT number): NCT02380053

Contact: William J Anderson, MBCHB 00441382383902
Contact: Ashley E Morrison, MSc 00441382383902

United Kingdom
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee Recruiting
Dundee, United Kingdom, DD1 9SY
Principal Investigator: William J Anderson, MBChB         
Sponsors and Collaborators
University of Dundee
Principal Investigator: William J Anderson, MBCHB University of Dundee / NHS Tayside

Responsible Party: William J Anderson, Consultant Respiratory Physician and Honorary Senior Lecturer, University of Dundee Identifier: NCT02380053     History of Changes
Other Study ID Numbers: CPET1
2015-000207-13 ( EudraCT Number )
2012RC22 ( Other Identifier: Sponsor (NHS Tayside/University of Dundee) )
First Posted: March 5, 2015    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017

Keywords provided by William J Anderson, University of Dundee:
Cardiopulmonary exercise testing

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Antihypertensive Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Vasodilator Agents