跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT01536587
NCT01536587已完成4 期

Effects of Bronchodilatation With Salmeterol on the Autonomic Nervous System

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2012年7月最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
32
试验地点
1
主要终点
Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
Single (Participant)

入排标准

年龄范围
41 Years 至 79 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •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

排除标准

  • •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

研究组 & 干预措施

Single Arm

Other

Inhalation of salmeterol 50 µg twice daily over 4 weeks

干预措施: Salmeterol (Drug)

结局指标

主要结局

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

时间窗: 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).

次要结局

  • Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4(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)(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0)(Baseline and 2 hours (Week 0))
  • Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4(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-MSNA Population)(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)(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)(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)(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)(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)(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)(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)(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)(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4(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)(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)(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)(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)(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)(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)(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)(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(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4(Baseline, 2 hours (Week 0), and Week 4)
  • Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4(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(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(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(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(Baseline and Week 4)
  • Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4(Baseline and Week 4)
  • Arterial Stiffness at Baseline (Week 0) and at Week 4(Baseline and Week 4)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

Loading locations...

相似试验

进行中（未招募）
不适用
Effects of bronchodilatation with salmeterol on the autonomic nervous systemChronic Obstructive Pulmonary Disease (COPD)MedDRA version: 14.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
EUCTR2011-001581-18-DEGlaxoSmithKline GmbH & Co. KG
已完成
不适用
Bronchodilator effects of salmeterol/fluticasone propionate (SFC) in patients with COPDCOPD
JPRN-UMIN000002764Atami Hospita International University of Health and Welfare30
尚未招募
不适用
Characterisation of lung function in chronic obstructive pulmonary disease (COPD) and asthma patients using a new lung imaging technique.Chronic Obstructive Pulmonary DiseaseAsthma
ACTRN12619000447156Woolcock Institute of Medical Research70
进行中（未招募）
不适用
Comparison of standard and novel, double-active medications used to expand bronchi in diagnostic test in patients suffering from chronic lung disease (chronic obstructive pulmonary disease COPD and asthma).COPD (chronic obstructive pulmonary disease)
EUCTR2014-002667-15-ATMedizinische Universität Innsbruck, Innere Medizin VI
已完成
不适用
Additive effects of short-acting bronchodilators in COPD patients who still had dyspnea in their daily lives despite long-acting bronchodilators.Chronic obstructive pulmonary disease
JPRN-UMIN000003192Department of Biomedical Laboratory Sciences, Shinshu University School of Health Sciences.60