NCT00671151

Brief 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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jun 2005

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2005

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2007

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

April 30, 2008

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 5, 2008

Completed
Last Updated

May 5, 2008

Status Verified

April 1, 2008

Enrollment Period

2.5 years

First QC Date

April 30, 2008

Last Update Submit

May 2, 2008

Conditions

COPD

Keywords

COPD exacerbationhistonesteroid resistanceinflammationtheophylline

Outcome Measures

Primary Outcomes (1)

  • HDAC activity in alveolar macrophages

    3 months

Secondary Outcomes (2)

  • Lung function

    3 months

  • Inflammatory cytokine release in sputum and serum

    3 months

Study Arms (2)

1

ACTIVE COMPARATOR

Low-dose theophylline on top of standard therapy for COPD exacerbation

Drug: Theophylline

2

NO INTERVENTION

Standard therapy for COPD exacerbation

Interventions

TheophyllineDRUG

Theophylline 100 mg bid for 3 months

1

Eligibility Criteria

Age40 Years - 75 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Universitario Son Dureta

Palma de Mallorca, Balearic Islands, 07014, Spain

Location

Related Publications (2)

  • 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. doi: 10.1084/jem.20040416. Epub 2004 Aug 30.

    PMID: 15337792BACKGROUND

  • Cosio BG, Iglesias A, Rios A, Noguera A, Sala E, Ito K, Barnes PJ, Agusti A. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax. 2009 May;64(5):424-9. doi: 10.1136/thx.2008.103432. Epub 2009 Jan 21.

    PMID: 19158122DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic ObstructiveInflammation

Interventions

Theophylline

Condition Hierarchy (Ancestors)

Lung Diseases, ObstructiveLung DiseasesRespiratory Tract DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

XanthinesAlkaloidsHeterocyclic CompoundsPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Borja G Cosio, MD

    Hospital Universitario Son Dureta

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

April 30, 2008

First Posted

May 5, 2008

Study Start

June 1, 2005

Primary Completion

December 1, 2007

Study Completion

December 1, 2007

Last Updated

May 5, 2008

Record last verified: 2008-04

Locations

ES(1)