Theophylline in Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Collaborator:
Ontario Lung Association
Information provided by:
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00299858
First received: March 3, 2006
Last updated: November 10, 2010
Last verified: November 2010
  Purpose

This will be a prospective randomized double-blinded parallel group clinical trial evaluating the short-term effects of theophylline therapy on exercise duration and lung function in patients with chronic obstructive pulmonary disease already receiving both tiotropium and a long-acting beta-agonist (salmeterol or formoterol).


Condition Intervention Phase
COPD
Drug: Theophylline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Theophylline on Exercise Capacity and Lung Function in COPD Patients Receiving Long-acting Inhaled Bronchodilator Therapy

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Exercise duration during constant load (75% maximum) exercise testing [ Time Frame: End of 4 week treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in spirometry (FEV1) Changes in lung volumes [ Time Frame: End of 4 week treatment period ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2006
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Study Group
Patients will be given theophylline, titrated to optimal blood levels, for a period of 4 weeks.
Drug: Theophylline

Patients assigned to study group, will receive slow-release theophylline at a dose of 10 mg/kg, titrated to blood levels between 55-110 umol/L, for a period of 4 weeks.

Patients assigned to placebo group will receive identical-appearing placebo tablets for the same period of time.

Placebo Comparator: Placebo group
Patients will receive placebo pills for a period of 4 weeks.
Drug: Theophylline

Patients assigned to study group, will receive slow-release theophylline at a dose of 10 mg/kg, titrated to blood levels between 55-110 umol/L, for a period of 4 weeks.

Patients assigned to placebo group will receive identical-appearing placebo tablets for the same period of time.


Detailed Description:

Objective:

The primary objectives of this study is to assess the effects of 4 weeks of theophylline therapy on exercise performance and lung function in patients with COPD already receiving combination inhaled long-acting bronchodilator therapy.

Background:

The latest Canadian COPD guidelines recommend the use of long-acting bronchodilators in patients who continue to experience symptoms despite as-needed use of short-acting bronchodilators. Unfortunately, patients with severe COPD may continue to experience symptoms despite use of both long-acting beta-agonists and anticholinergics. For these patients, the Canadian guidelines recommend a trial of theophylline. Studies have shown that theophylline can reduce symptoms and improve exercise performance, however, the use of theophylline is limited by its narrow therapeutic window and multiple drug interactions. Despite recommendations, it remains unknown whether theophylline provides any additional benefit for COPD patients already receiving combined long-acting bronchodilator therapy. No study has evaluated the effect of theophylline in patients already receiving both long-acting beta-agonist and long-acting anticholinergic therapy.

Methods:

This will be a prospective randomized double-blinded parallel group clinical trial evaluating the short-term effects of theophylline therapy on exercise duration and lung function in patients already receiving both tiotropium and a long-acting beta-agonist (salmeterol or formoterol). Twenty-four patients with moderate to severe COPD who are already using tiotropium and long-acting beta agonists will be randomized to receive either: a) 4 weeks of oral theophylline dosed to achieve therapeutic blood levels, or b) 4 weeks of identical placebo therapy. Only patients with stable COPD (no exacerbations nor changes in medications over the last 2 months) and no contraindications to exercise testing or theophylline use will be enrolled. All patients will undergo baseline pulmonary function testing and incremental and constant load exercise testing prior to randomization. PFTs and constant load exercise testing will be repeated after 4 weeks of therapy. Patients will be instructed to report adverse events and will have their theophylline dose adjusted to ensure therapeutic bloods levels (55-110 umol/L), prior to repeat testing.

Outcome Measurements:

The primary outcome of interest will be the effect of theophylline on exercise duration during constant load (75% maximum) exercise testing. The study will be powered to detect a 20% greater improvement in exercise duration for the theophylline-treated group. Secondary outcome measures will include changes in spirometry (FEV1) and lung volumes.

Anticipated results:

Exercise duration (on constant load exercise testing) was chosen as the primary endpoint of this study because it has been shown to be a reproducible and highly responsive measure for physiologic benefit in COPD. It is unknown whether theophylline will provide any additional increase in exercise duration, when added to a combined long-acting bronchodilator regimen. If an improvement is found with theophylline, a follow-up study of larger size and longer duration will be required to investigate whether this benefit will translate into improvements in clinical outcomes such as quality of life or frequency of exacerbations. Alternatively, if no improvement can be detected, the current COPD treatment recommendation should be re-evaluated.

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

clinical diagnosis of COPD, that is at least "moderate" in severity according to GOLD guidelines (FEV1 60% predicted and FEV1/FVC ratio 70%).

clinically stable (no exacerbations nor changes in medications over the previous two months.

taking tiotropium 18ug qd and either salmeterol 50ug bid or formoterol 12 ug bid (the use of inhaled corticosteroids is not required but is permitted as long as there have been no dose changes over the last 2 months).

Exclusion Criteria:

Lung disease other than COPD (e.g: asthma, interstitial lung disease)

Non-pulmonary comorbidity that may potentially limit exercise capacity (e.g: cardiac disease, arthritis) or be exacerbated by theophylline use.

History of adverse response to theophylline or condition that may increase likelihood of adverse reaction with theophylline (cardiac disease, liver disease, renal impairment, thyroid disease)

Use of theophylline over last two months.

Use of a medication that may potentially interact with theophylline (e.g. warfarin, digoxin)

Patients currently enrolled (or scheduled to be enrolled) in a pulmonary rehabilitation program will not be accepted until after completion of the program (as this may potentially affect exercise performance).

Use of systemic corticosteroid therapy (this may affect peripheral muscle function)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00299858

Locations
Canada, Ontario
Ottawa Hospital, General campus
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
Ottawa Hospital Research Institute
Ontario Lung Association
Investigators
Principal Investigator: Nha Voduc, MD Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: Nha Voduc, University of Ottawa
ClinicalTrials.gov Identifier: NCT00299858     History of Changes
Other Study ID Numbers: 2006036-01H
Study First Received: March 3, 2006
Last Updated: November 10, 2010
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Chronic Obstructive Pulmonary Disease
Theophylline
Exercise testing

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Theophylline
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 26, 2014