Pulmonary Disease, Chronic ObstructivePhase 1NCT00116402

A Pilot Study of the Mechanism of Synergism Between FP and Salmeterol in Preventing COPD Exacerbations

A Phase 1 study testing fluticasone and salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by University of Chicago at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment. Read more about this study

Who is it for?: Ages 50 years and older
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: fluticasone and salmeterol
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited States
Study dates: Jan 2005to Oct 2009
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males or females > 50 years of age
Physiologic evidence of COPD defined per ATS guidelines as: cigarette smoking history >20 pack years, FEV1/FVC <70%
Patients must have a post-bronchodilator FEV1 >50% of predicted value at enrollment
Patient must have an O2 saturation measure by pulse oximetry >90% on RA
Must be able to participate in the study, willing to give informed consent, and comply with the study restrictions

Who cannot join

Women of child-bearing potential defined as females who are less than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy
Observation of any solitary nodule in the lung requiring further medical intervention
Patients on maintenance therapy with oral steroids
Patients with giant bullous disease
Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient's ability to perform the study tests
Presence of a coagulopathy as defined by a platelet count <100,000/mm3, and PT and PTT >1.2 x the upper limit of normal

Show all 11Show fewer

Concurrent enrollment or participation in any other clinical trials within the past 30 days
Primary diagnosis of asthma
History of alpha 1 antitrypsin deficiency
Any clinically significant and active pulmonary disease that could contribute to dyspnea
Current systemic and inhaled steroids and theophylline

Trial locations and contacts

1 site in 1 country.

United States1 site

Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago
Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: A Pilot Study of the Mechanism of Synergism Between Fluticasone (FP) and Salmeterol in Preventing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment.

Read the detailed description

Our objective is to examine the mechanism of the additive/synergistic properties of b2-adrenoceptor stimulation and corticosteroid receptor activation in:

Preventing neutrophil adhesion to specific endothelial ligands, e.g. ICAM-1 and
Undergoing activation as a consequence of this adhesion.

We hypothesize that combination therapy with salmeterol + fluticasone (FP) will:

Augment the inhibition of adhesion of neutrophils obtained from the peripheral blood of study subjects in vitro, by blocking gIV-PLA2 translocation to the nuclear membrane as for eosinophils;
Augment the inhibition of transendothelial migration of neutrophils into airways of subjects with chronic obstructive pulmonary disease;
Augment the numbers and concentrations of pro-inflammatory products in the bronchoalveolar lavage fluid; and
Decrease the number of neutrophils in the bronchial tissue of endobronchial biopsies of treated patients.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: fluticasone and salmeterol
Keywords: COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy
Medical subject headings: Pulmonary Disease, Chronic Obstructive, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

fluticasone and salmeterolDrug
1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.

Study groups in NCT00116402
Study group	Role	What they receive
1	Active comparator	will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID Receives: Drug: fluticasone and salmeterol
2	Active comparator	salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID Receives: Drug: fluticasone and salmeterol

What is being measured

The primary outcome is the main question the study is designed to answer.

To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2005Oct 2009

First posted29 Jun 2005 (estimated)
Study startJan 2005
Primary completionSep 2009
Study completionOct 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by University of ChicagoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00116402
Sponsor's protocol ID: 13426B
Status last verified: Aug 2014
First submitted: 28 Jun 2005
Last updated: 5 Aug 2014
Results posted: No
Data monitoring committee: Yes

Publications

Soriano JB, Kiri VA, Pride NB, Vestbo J. Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patients. Am J Respir Med. 2003;2(1):67-74. doi: 10.1007/BF03256640.
PubMed 14720023
Hanania NA, Darken P, Horstman D, Reisner C, Lee B, Davis S, Shah T. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest. 2003 Sep;124(3):834-43. doi: 10.1378/chest.124.3.834.
PubMed 12970006
Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592-6. doi: 10.1164/rccm.2105025.
PubMed 12070058
Kim KP, Rafter JD, Bittova L, Han SK, Snitko Y, Munoz NM, Leff AR, Cho W. Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J Biol Chem. 2001 Apr 6;276(14):11126-34. doi: 10.1074/jbc.M004604200. Epub 2000 Dec 15.
PubMed 11118430
Kim YJ, Kim KP, Han SK, Munoz NM, Zhu X, Sano H, Leff AR, Cho W. Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2. J Biol Chem. 2002 Sep 27;277(39):36479-88. doi: 10.1074/jbc.M205399200. Epub 2002 Jul 17.
PubMed 12124392
Chang PS, Absood A, Linderman JJ, Omann GM. Magnetic bead isolation of neutrophil plasma membranes and quantification of membrane-associated guanine nucleotide binding proteins. Anal Biochem. 2004 Feb 15;325(2):175-84. doi: 10.1016/j.ab.2003.10.039.
PubMed 14751252
Myou S, Zhu X, Boetticher E, Myo S, Meliton A, Lambertino A, Munoz NM, Leff AR. Blockade of focal clustering and active conformation in beta 2-integrin-mediated adhesion of eosinophils to intercellular adhesion molecule-1 caused by transduction of HIV TAT-dominant negative Ras. J Immunol. 2002 Sep 1;169(5):2670-6. doi: 10.4049/jimmunol.169.5.2670.
PubMed 12193740
Reumaux D, de Boer M, Meijer AB, Duthilleul P, Roos D. Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. J Leukoc Biol. 2003 Jun;73(6):841-9. doi: 10.1189/jlb.1102567.
PubMed 12773517
Zhu X, Munoz NM, Kim KP, Sano H, Cho W, Leff AR. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J Immunol. 1999 Sep 15;163(6):3423-9.
PubMed 10477614
Meliton AY, Munoz NM, Liu J, Lambertino AT, Boetticher E, Myo S, Myou S, Zhu X, Johnson M, Leff AR. Blockade of LTC4 synthesis caused by additive inhibition of gIV-PLA2 phosphorylation: Effect of salmeterol and PDE4 inhibition in human eosinophils. J Allergy Clin Immunol. 2003 Aug;112(2):404-10. doi: 10.1067/mai.2003.1637.
PubMed 12897749
Reid DW, Ward C, Wang N, Zheng L, Bish R, Orsida B, Walters EH. Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J. 2003 Jun;21(6):994-9. doi: 10.1183/09031936.03.00109702.
PubMed 12797494
Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Oct 15;168(8):968-75. doi: 10.1164/rccm.200208-794OC. Epub 2003 Jul 11.
PubMed 12857718

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study of the Mechanism of Synergism Between Fluticasone (FP) and Salmeterol in Preventing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
ClinicalTrials.gov ID: NCT00116402
Acronym / sponsor ID: 13426B
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: University of ChicagoUniversity, hospital or other
Collaborators: GlaxoSmithKline
Study start: Jan 2005
Primary completion: Sep 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 29 Jun 2005 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment.

Detailed description

Our objective is to examine the mechanism of the additive/synergistic properties of b2-adrenoceptor stimulation and corticosteroid receptor activation in:

Preventing neutrophil adhesion to specific endothelial ligands, e.g. ICAM-1 and
Undergoing activation as a consequence of this adhesion.

We hypothesize that combination therapy with salmeterol + fluticasone (FP) will:

Augment the inhibition of adhesion of neutrophils obtained from the peripheral blood of study subjects in vitro, by blocking gIV-PLA2 translocation to the nuclear membrane as for eosinophils;
Augment the inhibition of transendothelial migration of neutrophils into airways of subjects with chronic obstructive pulmonary disease;
Augment the numbers and concentrations of pro-inflammatory products in the bronchoalveolar lavage fluid; and
Decrease the number of neutrophils in the bronchial tissue of endobronchial biopsies of treated patients.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Active comparator	Drug: fluticasone and salmeterolwill start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
2	Active comparator	Drug: fluticasone and salmeterolsalmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Males or females > 50 years of age
Physiologic evidence of COPD defined per ATS guidelines as: cigarette smoking history >20 pack years, FEV1/FVC <70%
Patients must have a post-bronchodilator FEV1 >50% of predicted value at enrollment
Patient must have an O2 saturation measure by pulse oximetry >90% on RA
Must be able to participate in the study, willing to give informed consent, and comply with the study restrictions

Key exclusion criteria (11 listed)

Women of child-bearing potential defined as females who are less than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy
Observation of any solitary nodule in the lung requiring further medical intervention
Patients on maintenance therapy with oral steroids
Patients with giant bullous disease
Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient's ability to perform the study tests

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
fluticasone and salmeterol1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID 2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.	Drug	1, 2

Primary outcome

To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD
Time frame: 12 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2014.
Background: PubMed 14720023Soriano JB, Kiri VA, Pride NB, Vestbo J. Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patients. Am J Respir Med. 2003;2(1):67-74. doi: 10.1007/BF03256640.
Background: PubMed 12970006Hanania NA, Darken P, Horstman D, Reisner C, Lee B, Davis S, Shah T. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest. 2003 Sep;124(3):834-43. doi: 10.1378/chest.124.3.834.
Background: PubMed 12070058Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592-6. doi: 10.1164/rccm.2105025.
Background: PubMed 11118430Kim KP, Rafter JD, Bittova L, Han SK, Snitko Y, Munoz NM, Leff AR, Cho W. Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J Biol Chem. 2001 Apr 6;276(14):11126-34. doi: 10.1074/jbc.M004604200. Epub 2000 Dec 15.
Background: PubMed 12124392Kim YJ, Kim KP, Han SK, Munoz NM, Zhu X, Sano H, Leff AR, Cho W. Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2. J Biol Chem. 2002 Sep 27;277(39):36479-88. doi: 10.1074/jbc.M205399200. Epub 2002 Jul 17.
Background: PubMed 14751252Chang PS, Absood A, Linderman JJ, Omann GM. Magnetic bead isolation of neutrophil plasma membranes and quantification of membrane-associated guanine nucleotide binding proteins. Anal Biochem. 2004 Feb 15;325(2):175-84. doi: 10.1016/j.ab.2003.10.039.
Background: PubMed 12193740Myou S, Zhu X, Boetticher E, Myo S, Meliton A, Lambertino A, Munoz NM, Leff AR. Blockade of focal clustering and active conformation in beta 2-integrin-mediated adhesion of eosinophils to intercellular adhesion molecule-1 caused by transduction of HIV TAT-dominant negative Ras. J Immunol. 2002 Sep 1;169(5):2670-6. doi: 10.4049/jimmunol.169.5.2670.
Background: PubMed 12773517Reumaux D, de Boer M, Meijer AB, Duthilleul P, Roos D. Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. J Leukoc Biol. 2003 Jun;73(6):841-9. doi: 10.1189/jlb.1102567.
Background: PubMed 10477614Zhu X, Munoz NM, Kim KP, Sano H, Cho W, Leff AR. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J Immunol. 1999 Sep 15;163(6):3423-9.
Background: PubMed 12897749Meliton AY, Munoz NM, Liu J, Lambertino AT, Boetticher E, Myo S, Myou S, Zhu X, Johnson M, Leff AR. Blockade of LTC4 synthesis caused by additive inhibition of gIV-PLA2 phosphorylation: Effect of salmeterol and PDE4 inhibition in human eosinophils. J Allergy Clin Immunol. 2003 Aug;112(2):404-10. doi: 10.1067/mai.2003.1637.
Background: PubMed 12797494Reid DW, Ward C, Wang N, Zheng L, Bish R, Orsida B, Walters EH. Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J. 2003 Jun;21(6):994-9. doi: 10.1183/09031936.03.00109702.
Background: PubMed 12857718Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Oct 15;168(8):968-75. doi: 10.1164/rccm.200208-794OC. Epub 2003 Jul 11.

Related trials for Pulmonary Disease, Chronic Obstructive

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Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Imre Noth, M.D. principal investigator

University of Chicago

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing fluticasone and salmeterol in people with Pulmonary Disease, Chronic Obstructive, run by University of Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00116402, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2014.