Effects of Salmeterol on Autonomic Nervous System (ESAN)
This study has been completed.
Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01536587
First received: February 2, 2012
Last updated: February 28, 2013
Last verified: February 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Disease, Chronic Obstructive |
Drug: Salmeterol |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment |
| Official Title: | Effects of Bronchodilatation With Salmeterol on the Autonomic Nervous System |
Resource links provided by NLM:
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
- Change in Muscle Sympathetic Nerve Activity (MSNA) [ Time Frame: baseline and 2 hours ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Change in Muscle Sympathetic Nerve Activity (MSNA) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in Heart Rate Variability (HRV) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in spontaneous baroreflex sensitivity [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in forced expiratory volume in one second (FEV1) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in vital capacity (VC) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in functional residual capacity (FRC) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in total lung capacity (TLC) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in residual volume (RV) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in norepinephrine [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in epinephrine [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in Brain Natriuretic Peptide (BNP) [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
- Change in arterial stiffness [ Time Frame: baseline and 4 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 34 |
| Study Start Date: | July 2012 |
| Study Completion Date: | November 2012 |
| Primary Completion Date: | November 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Single Arm
Inhalation of salmeterol 50 µg twice daily over 4 weeks
|
Drug: Salmeterol
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.
|
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.
Eligibility| Ages Eligible for Study: | 41 Years to 79 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations More Information
No publications provided
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT01536587 History of Changes |
| Other Study ID Numbers: | 114520 |
| Study First Received: | February 2, 2012 |
| Last Updated: | February 28, 2013 |
| Health Authority: | Germany: Bundesinstitut für Arzneimittel und Medizinprodukte |
Keywords provided by GlaxoSmithKline:
|
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, |
Additional relevant MeSH terms:
|
Chronic Disease Lung Diseases Respiration Disorders Pulmonary Disease, Chronic Obstructive Disease Attributes Pathologic Processes Respiratory Tract Diseases Lung Diseases, Obstructive Salmeterol Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists |
Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Anti-Asthmatic Agents Respiratory System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013