Nitric Oxyde Concentration in Chronic Obstructive Pulmonary Disease Patients - SANOB Study

NCT01853787 | Completed Phase 4 DMC

• 1 other identifier: 898CEC
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

• Among many other causes, Bronchial obstruction in Chronic Obstructive Pulmonary Disease (COPD) is also caused by inflammation of peripheral airways walls.
• Neutrophils and other inflammatory mediators like Interleukin-6 (IL6), Interleukin-8 (IL8), Interleukin-1 alpha (IL-1 alpha),Interleukin-1beta (IL-1 beta), Tumor Necrosis Factor alfa (TNF-alfa), Reactive Oxygen Species (ROS), Leukotriene B4 (LTB4), Nitric Oxyde (NO) are implicated in the inflammation.
• NO is produced in response to physical and chemical stress on bronchial epithelium and plays a critical role in small airways remodelling
• Exhaled NO concentration is usually used to monitor bronchial inflammation
• The relationship between stretch and strain of small airways and bronchial inflammation is not well understood.
• The investigators hypothesis is that cyclic opening and closure of peripheral obstructed airways through the consequent stretching and strain acting on them can provoke an inflammatory response which can be monitored by exhaled NO.
• The pharmacological effects of bronchodilators may play a role on bronchial inflammation by reducing the stretching stress on bronchiolar walls thus reducing the production of NO in exhalate
• Data about these physiopathological aspects is missing in literature.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; bronchial inflammation; NO concentration; small airways; LABA; Small Airways Stretching; Stretch and strain of small airways in COPD; Acute LABA effect on NO production; Pulmonary desufflation

Outcome Measures

Primary Outcomes (1)

• Change in exhaled Nitric Oxide concentration after Long acting Beta 2 Agonist assumption

  The evaluation of exhaled Nitric Oxide concentration will be performed following the schedule below: * at baseline (T0), after 72 hours of inhalatory therapy washout * 30 minutes (T1) after the assumption of a inhaled bronchodilator (Salmeterol 50 mcg or Formoterol 12 mcg) * 60 minutes after T0 (T2) * 180 minutes after T0 (T3) every patient will repeat the same four steps in two different days after 72 hours of pharmacological washout, crossing over in blind conditions the bronchodilator taken the previous study day. The measurements of Exhaled NO will be performed by Medi-Soft Exp'air FeNo concentration sampling device, Sorinnes (Dinant) Belgium. At every step, will be performed 3 measurements at different flows (50 ml/sec, 100 ml/sec, 150 ml/sec and 350 ml/sec), for a total of 12 valid measurements for each step. Alveolar NO and Bronchial Wall NO concentrations will be taken in consideration.

  - At baseline, after 30 minutes of LABA assumption, after 60 minutes of LABA assumption, after 180 minutes of LABA assumption

Secondary Outcomes (5)

• Change in static plethysmographic volumes, assessment of desufflation and resistances after Long acting Beta 2 Agonist assumption and

  At baseline, after 30 minutes of LABA assumption, after 60 minutes of LABA assumption, after 180 minutes of LABA assumption

• Diffusion Lung Capacity for Carbon Monoxide (DLCO) and Alveolar Volume (VA) variation from baseline

  At baseline, after 30 minutes of LABA assumption, after 60 minutes of LABA assumption, after 180 minutes of LABA assumption

• Modification of arterial gases concentration after bronchodilator therapy in acute conditions

  At baseline, after 180 minutes of LABA assumption

• Closing Capacity variability from baseline at the Single Breath Nitrogen Washout test

  At baseline, after 30 minutes of LABA assumption, after 60 minutes of LABA assumption, after 180 minutes of LABA assumption

• Change from baseline in dyspnoea, evaluated with VAS (Visual Analogue Scale).

  At baseline, after 30 minutes of LABA assumption, after 60 minutes of LABA assumption, after 180 minutes of LABA assumption

Study Arms (2)

Formoterol Fumarate

EXPERIMENTAL

At study day n°1 the patients will be randomized to take either Salmeterol or Formoterol in a double blind way.

Drug: Formoterol Fumarate; Drug: Salmeterol

Salmeterol

ACTIVE COMPARATOR

The second study arm represents the crossing over arm. Every patient, at study day number 2 will take a different medication (Salmeterol 50 mcg or Formoterol 12 mcg) from that taken at the study day n° 1.

Drug: Formoterol Fumarate; Drug: Salmeterol

Interventions

Formoterol Fumarate DRUG

Formoterol Fumarate, one inhalation of 12 mcg via MDI (Metered Dose Inhaler) Modulite will be taken in double blind randomized way immediately after T0 evaluation.

Also known as: Foradil spray, Novartis Farma S.p.A.

Formoterol Fumarate; Salmeterol

Salmeterol DRUG

Salmeterol 50 mcg via MDI (Metered Dose Inhaler), one inhalation only, immediately after T0 evaluation

Also known as: Serevent, GlaxoSmithKline S.p.A.

Formoterol Fumarate; Salmeterol

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signature of informed consent
• COPD patients with age raging from 50 to 85 years old
• Patients with at least a history of COPD of one year
• COPD patients clinically stable in the last three months
• COPD subjects with FEV1 (Forced Expiratory Volume in 1st second)\<70% of predicted value
• FEV1/FVC (Forced Expiratory Volume in 1st second/Forced Vital Capacity) \<88% (males) or \<89% (females) of LLN (Low Levels of Normality)
• COPD former or active smokers with at least a smoking history of 20 pack year

You may not qualify if:

• Acute Bronchial Exacerbation at recruitment
• Fertile women with age between 18 and 50 years old or with active period
• Pregnancy
• Subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment.
• FEV1/FVC more than 70% of predicted value in basal conditions
• FEV1 more than 70% of predicted value in basal conditions
• Known deficit of alpha 1 antitrypsin
• Subjects that underwent a Lung Volume Reduction Surgery (LVRS)
• Subjects with known positivity to Human Immunodeficiency Virus (HIV)
• Misuse of alcool or drugs
• Lack of compliance in performing respiratory tests
• Subjects not capable to follow the study prescriptions because of psychic disorders or language problems.
• Long Term Oxygen Therapy with flows \> 6 litres per minute (l/min) at rest

Sponsors & Collaborators

• University of Milan: lead
• Fondazione Salvatore Maugeri: collaborator
• Università degli Studi di Ferrara: collaborator

Study Sites (2)

Clinica di Malattie dell'Apparato Respiratorio, Dipartimento di Scienze Mediche, Università di Ferrara

Ferrara, Ferrara, 44121, Italy

Location

: Pneumologia Riabilitativa-Fondazione Maugeri-Istituto Scientifico di Milano- IRCCS

Milan, Milano, 20138, Italy

Location

Related Publications (1)

• Santus P, Radovanovic D, Mascetti S, Pauletti A, Valenti V, Mantero M, Papi A, Contoli M. Effects of bronchodilation on biomarkers of peripheral airway inflammation in COPD. Pharmacol Res. 2018 Jul;133:160-169. doi: 10.1016/j.phrs.2018.05.010. Epub 2018 May 23.

  PMID: 29775687 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Formoterol Fumarate; 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)

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

Study Officials

• Pierachille santus, Md, PhD

  Università degli Studi di Milano-Pneumologia Riabilitativa-Fondazione Salvatore Maugeri-MILANO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pulmonary Rehabilitation Unit

Study Record Dates

• First Submitted: May 5, 2013
• First Posted: May 15, 2013
• Study Start: July 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 10, 2015

Record last verified: 2015-07

Locations

IT (2)