Effects of Salmeterol on Autonomic Nervous System
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: Salmeterol
Intervention description: At visit 1 the sympathetic activity will be registered using microneurographic recordings of efferent muscle sympathetic nerve activity (MSNA) in the peroneal nerve and respiration over 2 hours, after 20 minutes of recording, 1 dose of placebo will be administered and after a further recording period of 45 minutes a dose of salmeterol 50 µg will be administered which will be followed by a further period of data registration. At visit 2 following 4 weeks of inhaled treatment with salmeterol the same procedures will be performed but a placebo inhalation will not be performed.
Intervention MeSH terms: Salmeterol Xinafoate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: Single (Participant)
Enrollment: 32.0
Sex: All
Minimum age: 41 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: influence of bronchodilatation with salmeterol on the autonomic nervous systems in COPD patients will be measured using MSNA.; Relation of COPD and sympathetic nerve activity is to be evaluated,

Summary:

      This is a 4-week non-randomized, partially blinded, single-arm monocentre study in subjects
      with Chronic Obstructive Pulmonary Disease (COPD) Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) class II or III with the aim to demonstrate that inhaled therapy with
      salmeterol reduces sympathetic activity as evaluated by microneurography. A maximum of 32
      subjects is planned to be enrolled.
    

Eligibility criteria:

        Inclusion Criteria:

          -  COPD of GOLD Class II or III with a post-bronchodilator spirometry forced expiratory
             volume in one second (FEV1) <60% predicted and FEV1/vital capacity (VC) <70% in
             accordance with the GOLD executive summary

          -  Subject is ambulatory (outpatient)

          -  Subject is therapy-naive (defined as not receiving any previous regular COPD therapy)

          -  Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at
             Screening Visit. Previous smokers are defined as those who have stopped smoking for at
             least 1 month prior to Visit 1

          -  Willing to participate in the study, must be able to inhale study medication

        Exclusion Criteria:

          -  Women who are pregnant or lactating

          -  Subjects not willing or unable to sign the informed consent before study start

          -  diagnosis of asthma

          -  α-1 antitrypsin deficiency

          -  active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis,
             pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases

          -  Subjects with lung volume reduction surgery within the 12 months prior to Screening

          -  Subjects who have been hospitalized due to poorly controlled COPD within 6 weeks prior
             to the Screening Visit

          -  Subjects with poorly controlled COPD, defined as the occurrence of an exacerbation
             managed with systemic corticosteroids or antibiotics prescribed by a physician 6 weeks
             prior to the Screening Visit

          -  Frequent exacerbations necessitating the therapy with inhaled glucocorticosteroids
             according to the GOLD guideline

          -  COPD with nasal intermittent positive pressure ventilation (NIPPV)

          -  Treatment with drugs having direct sympathomimetic activity (e.g. theophylline,
             moxonidine, clonidine), Oral medication with beta2-sympathomimetics

          -  Inhaled therapy with anti-cholinergics, sodium cromoglycate or nedocromil sodium

          -  Treatment with systemic, oral or parenteral (intra-articular) corticosteroids

          -  Treatment with strong cytochrome P450 3A4 inhibitors

          -  Treatment with any other investigational drug

          -  Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or
             nocturnal oxygen therapy required for greater than 12 hours a day

          -  Subjects who are medically unable to withhold their short-acting beta-agonist (SABA)
             for the 6-hour period required prior to spirometry testing at each study visit

          -  Subjects with clinically significant sleep apnoea that is uncontrolled

          -  Unstable angina pectoris or signs and history of left heart failure with a left
             ventricular ejection fraction <40%

          -  Arterial hypertension necessitating treatment with >1 antihypertensive drug

          -  Clinically evident polyneuropathy

          -  Diabetes mellitus necessitating any pharmacological therapy

          -  Severe concomitant disease (likely to reduce life expectancy to less than 3 years)

          -  Other diseases/abnormalities: Subjects with historical or current evidence of
             clinically significant neurological, psychiatric, renal, hepatic, immunological,
             endocrine or haematological abnormality that is uncontrolled