Effects of Low-Dose Theophylline During Chronic Obstructive Pulmonary Disease (COPD) Exacerbations - Full Text View

Sponsors and Collaborators:	Hospital Universitari Son Dureta Fondo de Investigación Sanitaria (FIS) Sociedad Española de Neumología y Cirugía Torácica
Information provided by:	Hospital Universitari Son Dureta
ClinicalTrials.gov Identifier:	NCT00671151

Purpose

Molecular mechanisms of COPD exacerbations and the modulating effect of low dose theophylline on that inflammation are elucidated in this project.

NF-kappa B-dependent pathway and acetylation status of nuclear histones are to be studied.Design: controlled, prospective and randomized study with or without theophylline, a potent HDAC activator.Objectives: 1) To determine NF-kB activation, histone deacetylase (HDAC) and histone acetyl-transferase (HAT) activity in sputum macrophages and blood monocytes during an episode of exacerbation and 3 months later, once stability is achieved. To correlate these measurements with inflammatory and oxidative stress markers and with pulmonary function and clinical variables. 2) To assess the effect of theophylline on previous molecular, functional and clinical data. Method: 25 patients with COPD will be recruited during an episode of exacerbation requiring hospitalization. NF-kB activation, HDAC and HAT activity, markers of inflammation and oxidative stress will be determined with specific assays.

These determinations will be repeated once the patient is stable and compared with smokers and non smoker controls with normal lung function

Condition	Intervention
COPD	Drug: Theophylline

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Single Blind (Outcomes Assessor), Active Control, Single Group Assignment
Official Title:	Molecular Mechanisms of COPD Exacerbations. Effect of Low-Dose Theophylline

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Theophylline Theophylline sodium glycinate

U.S. FDA Resources

Further study details as provided by Hospital Universitari Son Dureta:

Primary Outcome Measures:

HDAC activity in alveolar macrophages [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Lung function [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Inflammatory cytokine release in sputum and serum [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment:	35
Study Start Date:	June 2005
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Low-dose theophylline on top of standard therapy for COPD exacerbation	Drug: Theophylline Theophylline 100 mg bid for 3 months
2: No Intervention Standard therapy for COPD exacerbation

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Severe COPD according to GOLD guidelines
Age between 40 and 75
Admission to hospital due to COPD exacerbation

Exclusion Criteria:

History of asthma
Pulmonary embolism
Pneumonia
Other chronic inflammatory disease
Patient on theophylline at the time of admission
Patient on oral steroids at the time of admission

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671151

Locations

Spain, Baleares
Hospital Universitario Son Dureta
Palma de Mallorca, Baleares, Spain, 07014

Sponsors and Collaborators

Hospital Universitari Son Dureta

Fondo de Investigación Sanitaria (FIS)

Sociedad Española de Neumología y Cirugía Torácica

Investigators

Principal Investigator:

Borja G Cosio, MD

Hospital Universitario Son Dureta

More Information

Publications:

Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med. 2004 Sep 6;200(5):689-95. Epub 2004 Aug 30.

Responsible Party:	Specialist in Respiratory Medicine ( Borja G Cosio MD )
Study ID Numbers:	FIS042146
Study First Received:	April 30, 2008
Last Updated:	May 2, 2008
ClinicalTrials.gov Identifier:	NCT00671151 History of Changes
Health Authority:	Spain: Ethics Committee

Keywords provided by Hospital Universitari Son Dureta:

COPD exacerbation
histone
steroid resistance
inflammation
theophylline

Study placed in the following topic categories:

Vasodilator Agents
Lung Diseases, Obstructive
Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Lung Diseases
Anti-Asthmatic Agents

Cardiovascular Agents
Peripheral Nervous System Agents
Bronchodilator Agents
Theophylline
Inflammation
Pulmonary Disease, Chronic Obstructive

Additional relevant MeSH terms:

Respiratory System Agents
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Asthmatic Agents
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Lung Diseases, Obstructive

Phosphodiesterase Inhibitors
Respiratory Tract Diseases
Autonomic Agents
Lung Diseases
Therapeutic Uses
Peripheral Nervous System Agents
Bronchodilator Agents
Pulmonary Disease, Chronic Obstructive
Theophylline

ClinicalTrials.gov processed this record on July 02, 2009