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

COPD Clinical Trial

Official title:

Molecular Mechanisms of COPD Exacerbations. Effect of Low-Dose Theophylline

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671151
• Other study ID #: FIS042146
• Status: Completed
• Phase: N/A
• First received: April 30, 2008
• Last updated: May 2, 2008
• Start date: June 2005
• Est. completion date: December 2007

Study information

• Verified date: April 2008
• Source: Hospital Universitari Son Dureta
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• COPD
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Theophylline
Theophylline 100 mg bid for 3 months

Locations

Country	Name	City	State
Spain	Hospital Universitario Son Dureta	Palma de Mallorca	Baleares

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Universitari Son Dureta	Fondo de Investigación Sanitaria (FIS), Sociedad Española de Neumología y Cirugía Torácica

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HDAC activity in alveolar macrophages		3 months	No
Secondary	Lung function		3 months	No
Secondary	Inflammatory cytokine release in sputum and serum		3 months	No