Effects of Salmeterol on Autonomic Nervous System (ESAN)

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 4

Conditions

Pulmonary Disease, Chronic Obstructive

Treatments

Drug: Salmeterol

Study type

Interventional

Funder types

Industry

Identifiers

NCT01536587

114520

Details and patient eligibility

About

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.

Full 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.

Enrollment

32 patients

Sex

All

Ages

41 to 79 years old

Volunteers

No Healthy Volunteers

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