Effects of Salmeterol on Autonomic Nervous System

NCT01536587 | Completed Phase 4 Results

• 1 other identifier: 114520
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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 evaluated by microneurography. A maximum of 32 subjects is planned to be enrolled.

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,

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  Baseline 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 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 Population)

  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)

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

Study Arms (1)

Single Arm

OTHER

Inhalation of salmeterol 50 µg twice daily over 4 weeks

Drug: Salmeterol

Interventions

Salmeterol DRUG

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.

Single Arm

Eligibility Criteria

• Age: 41 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Göttingen, Lower Saxony, 37075, Germany

Location

Related Publications (1)

• 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.

  PMID: 25924990 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2012
• First Posted: February 22, 2012
• Study Start: July 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 11, 2014
• Results First Posted: February 4, 2014

Record last verified: 2014-03

Locations

DE (1)