Pulmonary Disease, Chronic ObstructivePhase 4ESANNCT01536587
Effects of Salmeterol on Autonomic Nervous System
A Phase 4 study testing Salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 41 to 79 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Salmeterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2012to Nov 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 41 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Bronchodilatation With Salmeterol on the Autonomic Nervous System
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.
Read the detailed description
This is a 4-week non-randomized, partially blinded, single-arm monocentre study in subjects with COPD 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.
During a complex data registration period comprising the continuous recording of muscle sympathetic nerve activity (MSNA) and respiration and of various other measurements at Visit 1, placebo and 50 μg of salmeterol via Diskus™ inhaler will be administered in a sequential design. Following Visit 1, the subjects will be treated with salmeterol 50 μg twice daily via Diskus inhaler for 4 weeks. At the Final Visit (Visit 2) the data registration period of Visit 1 will be repeated with the only difference that no placebo will be administered.
Further endpoints, besides the evaluation of MSNA, include heart rate variability (HRV), spontaneous baroreflex sensitivity and lung function parameters.
Study enrolment will be stopped when valid MSNA data on the immediate effect of inhalation (manoeuvres at Visit 1) are available for 24 subjects.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Salmeterol
- 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,
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalmeterolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Other | Inhalation of salmeterol 50 µg twice daily over 4 weeks Receives: Drug: Salmeterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0)
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per 100 heart beats [bursts/100 heart beats]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1).
Measured: Baseline and 2 hours (Week 0)
Secondary outcomes (33)
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per 100 heart beats (bursts/100 heart beats). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline and Week 4
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0)
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per minute [bursts/minute]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1).
Measured: Baseline and 2 hours (Week 0)
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per minute (bursts/minute). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
Heart rate variability (HRV) refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms^2). Change from Baseline were calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (N-N) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms2). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation), respectively.
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms^2). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms^2). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)*100). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)*100). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)*100). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)*100). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Measured: 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)
Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Measured: 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)
BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Measured: 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)
BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Measured: 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)
Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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)
Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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
Systolic and diastolic BP was manually measured. Change in BP after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4
Respiratory rate is defined as the number of breaths taken within a set amount of time (typically within 60 seconds). Change in respiratory rate after salmeterol inhalation is expressed in terms of respiratory rate (breaths) per minute (min). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4
Tidal volume is defined as the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied (normal value is approximately 500 milliliters or 7 milliliters per kilogram of body weight). Change in tidal volume after salmeterol inhalation is expressed in terms of milliliters (mL). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4
Respiratory minute volume is defined as the volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person's lungs per minute. Change in respiratory minute volume after salmeterol inhalation is expressed in terms of milliliters per minute (mL/min). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma norepinephrine) after salmeterol inhalation is expressed in terms of nanogramms per liter (ng/L). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma epinephrine) after salmeterol inhalation is expressed in terms of nanograms per milliliter (ng/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (BNP) after salmeterol inhalation is expressed in terms of picograms per milliliter (pg/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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
Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen. The percentage is called blood oxygen saturation, or SpO2. Change in SpO2 after salmeterol inhalation is expressed in terms of percent. Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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
Transcutaneous carbon dioxide monitoring is a noninvasive way of continuously measuring the tension of these gases in the skin. This methodology provides a continuous noninvasive estimation of the arterial CO2 value. Change in tCO2 after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 [Visit 1, after salmeterol inhalation]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Measured: 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
FVC is defined as the volume of air that can be forcibly blown out from the lungs after a full inspiration. FRC is defined as the volume of air present in the lungs, specifically the parenchyma tissues, at the end of a passive expiration. TLC is defined as the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to VC plus the RV and is approximately 5800 milliliters. RV is defined as the amount of gas remaining in the lungs at the end of a maximal exhalation. All parameters describing lung function are expressed in terms of liters (L). Lung function (FVC, FRC [body and helium], TLC, and RV) was evaluated at Baseline (Week 0, [Visit 1, before any inhalation]) and at Week 4 (Visit 2, after salmeterol inhalation).
Measured: Baseline and Week 4
Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4
Diastolic dysfunction refers to the decline in performance of one (usually the left ventricle) or both (left and right) ventricles during diastole. The number of participants with diastolic dysfunction on echocardiography was evaluated at Baseline (Week 0, [Visit 1, before any inhalation]) and at Week 4 (Visit 2, after salmeterol inhalation).
Measured: Baseline and Week 4
Arterial Stiffness at Baseline (Week 0) and at Week 4
Arterial stiffness occurs as a consequence of age and arteriosclerosis. Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. PWV was evaluated in terms of meters per second (m/s). PWV after salmeterol inhalation at Baseline (Week 0, [Visit 1, before any inhalation]) and at Week 4 (Visit 2, after inhalation of salmeterol) was assessed.
Measured: Baseline and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2012 (estimated)
- Study startJul 2012
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01536587
- Sponsor's protocol ID
- 114520
- Acronym
- ESAN
- Status last verified
- Mar 2014
- First submitted
- 2 Feb 2012
- Last updated
- 11 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Haarmann H, Mohrlang C, Tschiesner U, Rubin DB, Bornemann T, Ruter K, Bonev S, Raupach T, Hasenfuss G, Andreas S. Inhaled beta-agonist does not modify sympathetic activity in patients with COPD. BMC Pulm Med. 2015 Apr 30;15:46. doi: 10.1186/s12890-015-0054-7.
PubMed 25924990
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Bronchodilatation With Salmeterol on the Autonomic Nervous System
- ClinicalTrials.gov ID
- NCT01536587
- Acronym / sponsor ID
- ESAN / 114520
- Conditions
- Pulmonary Disease, Chronic Obstructive
- 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,
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 22 Feb 2012 (estimated)
- Results
- Posted 4 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a 4-week non-randomized, partially blinded, single-arm monocentre study in subjects with COPD 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.
During a complex data registration period comprising the continuous recording of muscle sympathetic nerve activity (MSNA) and respiration and of various other measurements at Visit 1, placebo and 50 μg of salmeterol via Diskus™ inhaler will be administered in a sequential design. Following Visit 1, the subjects will be treated with salmeterol 50 μg twice daily via Diskus inhaler for 4 weeks. At the Final Visit (Visit 2) the data registration period of Visit 1 will be repeated with the only difference that no placebo will be administered.
Further endpoints, besides the evaluation of MSNA, include heart rate variability (HRV), spontaneous baroreflex sensitivity and lung function parameters.
Study enrolment will be stopped when valid MSNA data on the immediate effect of inhalation (manoeuvres at Visit 1) are available for 24 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Other | Drug: SalmeterolInhalation of salmeterol 50 µg twice daily over 4 weeks |
Who may qualify
- Ages
- 41 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalmeterolAt 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. | Drug | Single Arm |
Primary outcome
Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0)
Time frame: Baseline and 2 hours (Week 0)
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per 100 heart beats [bursts/100 heart beats]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1).
33 secondary outcomes
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4
Time frame: Baseline and Week 4
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0)
Time frame: Baseline and 2 hours (Week 0)
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4
Time frame: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4
Time frame: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4
Time frame: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4
Time frame: Baseline, 2 hours (Week 0), and Week 4
Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline and Week 4
Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4
Time frame: Baseline and Week 4
Arterial Stiffness at Baseline (Week 0) and at Week 4
Time frame: Baseline and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25924990Haarmann H, Mohrlang C, Tschiesner U, Rubin DB, Bornemann T, Ruter K, Bonev S, Raupach T, Hasenfuss G, Andreas S. Inhaled beta-agonist does not modify sympathetic activity in patients with COPD. BMC Pulm Med. 2015 Apr 30;15:46. doi: 10.1186/s12890-015-0054-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0) (time frame: Baseline and 2 hours (Week 0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01536587, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2014.