Last updated: 11/07/2018 07:48:54

Effects of salmeterol on autonomic nervous systemESAN

GSK study ID
114520
See study documents
Clinicaltrials.gov ID
NCT01536587
See results summary
EudraCT ID
2011-001581-18
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Effects of bronchodilatation with salmeterol on the autonomic nervous system
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
Single (Participant)
Allocation:
Not applicable
Primary outcomes:

Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 hours (Week 0)

Timeframe: Baseline and 2 hours (Week 0)

Secondary outcomes:

Change from Baseline in MSNA (evaluated by microneurography as bursts/100 heart beats) at Week 4

Timeframe: Baseline and Week 4

Change from Baseline in MSNA (evaluated by microneurography as bursts/minute) at 2 hours (Week 0)

Timeframe: Baseline and 2 hours (Week 0)

Change from Baseline in MSNA (evaluated by microneurography as bursts/minute) at Week 4

Timeframe: Baseline and Week 4

Change from Baseline in heart rate variability (HRV): standard deviation of NN intervals (SDNN) at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): standard deviation of NN intervals (SDNN) at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): square root of the mean squared difference of successive NNs (RMSSD) at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): square root of the mean squared difference of successive NNs (RMSSD) at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): absolute low frequency (LF) power at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): absolute low frequency (LF) power at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): absolute high frequency (HF) power at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): absolute high frequency (HF) power at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): normalized low frequency (LF) power at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): normalized low frequency (LF) power at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): normalized high frequency (HF) power at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): normalized high frequency power (HF) at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): heart rate at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in heart rate variability (HRV): heart rate at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in spontaneous baroreflex sensitivity (BRS) at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in spontaneous baroreflex sensitivity (BRS) at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in forced expiratory volume in one second (FEV1) at 2 hours (Week 0) and at Week 4 (ITT Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in forced expiratory volume in one second (FEV1) at 2 hours (Week 0) and at Week 4 (ITT-MSNA Population)

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in systolic and diastolic blood pressure (BP) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in respiratory rate at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in tidal volume at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in respiratory minute volume at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in catecholamines (plasma norepinephrine) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in catecholamines (plasma epinephrine) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in catecholamines (brain natriuretic peptide [BNP]) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in oxygen saturation measured via pulse oxymetry (SpO2) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Change from Baseline in transcutaneous carbon dioxide (tCO2) at 2 hours (Week 0) and at Week 4

Timeframe: Baseline, 2 hours (Week 0), and Week 4

Lung function (forced vital capacity [FVC], functional residual capacity [FRC; body and helium], total lung capacity [TLC], and residual volume [RV]) at Baseline (Week 0) and at Week 4

Timeframe: Baseline and Week 4

Number of participants with diastolic dysfunction on echocardiography at Baseline (Week 0) and at Week 4

Timeframe: Baseline and Week 4

Arterial stiffness at Baseline (Week 0) and at Week 4

Timeframe: Baseline and Week 4

Interventions:
  • Drug: Salmeterol
    • Enrollment:
    32
    Primary completion date:
    2012-30-11
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Helge Haarmann,David Rubin,Uta Tschiesner,Cordula Mohrlang,Thore Bornemann,Karin Rüter,Slavtcho Bonev,Tobias Raupach,Gerd Hasenfuß,Stefan Andreas. Inhaled ß-agonist does not modify sympathetic activity in patients with COPD. BMC Pulm Med. 2015;15:46.
    Medical condition
    Pulmonary Disease, Chronic Obstructive
    Product
    salmeterol
    Collaborators
    Not applicable
    Study date(s)
    July 2012 to November 2012
    Type
    Interventional
    Phase
    4

    Participation criteria

    Sex
    Female & Male
    Age
    41 - 79 years
    Accepts healthy volunteers
    No
    • 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)
    • Women who are pregnant or lactating
    • Subjects not willing or unable to sign the informed consent before study start
    Inclusion and exclusion 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

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Goettingen, Niedersachsen, Germany, 37075
    Status
    Study Complete
    Contact us

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)
    Protocol
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2012-30-11
    Actual study completion date
    2012-30-11

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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