Muscle Dysfunction in Patients With Chronic Obstructive Lung Disease (COPD): the Role of Sympathetic Activation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tobias Raupach, University Medical Center Goettingen
ClinicalTrials.gov Identifier:
NCT01750489
First received: December 9, 2012
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

The objective of the project is to better understand the causes of exercise limitation, dyspnea and neurohumoral activation in patients with COPD. In particular, the investigators aim to explore the mutual interaction of neurohumoral activation and exercise limitation thereby focussing on differential effects of the peripheral muscle and the diaphragm.

Eventually the findings might influence treatment modalities. If sympathetic activation contributes to exercise limitation then drugs influencing the autonomic nervous system would be a reasonable therapeutic concept. If a reduction of sympathetic activity due to an alteration of the ergoreflex can be achieved by non-invasive ventilation this would help to improve dyspnea and exercise capacity.


Condition Intervention
Chronic Obstructive Pulmonary Disease
Device: non-invasive ventilation (NIV)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Skeletal and Respiratory Muscle Dysfunction in Patients With COPD: the Role of Sympathetic Activation

Resource links provided by NLM:


Further study details as provided by University Medical Center Goettingen:

Primary Outcome Measures:
  • muscle sympathetic nerve activity (MSNA) [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
    In a 90 minute microneurographic measurement muscle sympathetic nerve activity is assessed.

  • Arterial stiffness [ Time Frame: 90 min ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • VE/VCO2 [ Time Frame: During 8-15 minutes bicycle exercise ] [ Designated as safety issue: No ]

Study Start Date: August 2011
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: COPD
Experimental: COPD with non-invasive ventilation (NIV)
Starting non-invasive ventilation with the patient's own device during registration of MSNA.
Device: non-invasive ventilation (NIV)
No Intervention: Healthy control subjects

Detailed Description:

Our aim is to investigate whether reduced exercise capacity, increased respiratory drive and dyspnoea are linked to heightened sympathetic activation at rest and during exercise in patients with COPD. Furthermore, the effect of unloading the respiratory muscles by using non-invasive ventilation (NIV) will be assessed. Fifteen stable COPD patients without NIV will be matched to 15 healthy control subjects (with sufficient microneurography recording). Furthermore COPD patients on regular NIV will be studied. Each participant will undergo symptom limited bicycle exercise and a handgrip protocol. Microneurography will be used to quantify sympathetic activity by the transcutaneous registration of postganglionic sympathetic efferents.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Diagnosis of COPD II or III according to the GOLD guidelines
  • FEV1 of less than 60% of the predicted value
  • RV/TLC > 45%
  • Optimal stable medication according to the GOLD guidelines for at least 2 weeks
  • The last exacerbation must not be more recent than three weeks
  • Stable sinus rhythm
  • The subgroup on NIV should be stable on NIV for > 1 month

Exclusion Criteria:

  • not willing or unable to sign the informed consent before the study begins
  • Age under 30 or over 80 years
  • paO2< 55 mmHg or PaCO2 > 45 mmHg on arterial blood gas analysis (For patients on NIV, PaCO2 values of up to 55 mmHg are acceptable.)
  • Treatment with drugs having direct sympathomimetic activity (e.g. theophylline, moxonidine, clonidine)
  • Oral medication with beta2 sympathomimetics (therapy with long-acting inhaled beta2 sympathomimetics is permitted)
  • History of sleep apnoea or documented evidence of > 15 episodes of apneas and/or hypopnea per hour during sleep. An episode of apnea is defined as the cessation of inspiratory airflow for 10 s or more. Hypopnea is defined as a reduction in airflow (> 50%) lasting for more than 10 s in comparison with the maximum airflow recorded during the preceding breathing cycle.
  • Myocardial infarction (MI) or a coronary revascularization procedure within the previous 2 calendar months
  • Clinically evident polyneuropathy
  • Diabetes mellitus necessitating any pharmacologic therapy
  • Severe (i.e., life-limiting) concomitant disease, including life-threatening malignancy (cancer likely to reduce life expectancy to less than 5 years), acquired immune deficiency syndrome, or any other life-threatening disease.
  • Diuretics should not be taken before measurements
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01750489

Locations
Germany
Universitaetsmedizin Goettingen
Goettingen, Germany, 37075
Sponsors and Collaborators
University Medical Center Goettingen
Investigators
Principal Investigator: Stefan Andreas, Professor Universitaetsmedizin Goettingen
  More Information

Additional Information:
Publications:
Responsible Party: Tobias Raupach, Dr., University Medical Center Goettingen
ClinicalTrials.gov Identifier: NCT01750489     History of Changes
Other Study ID Numbers: RA1937/1-1
Study First Received: December 9, 2012
Last Updated: May 9, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by University Medical Center Goettingen:
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 29, 2014